The TP63-related disorders comprise a spectrum of overlapping autosomal dominant ectodermal dysplasia syndromes caused by heterozygous mutations in TP63, which encodes the transcription factor p63. Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation or syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. The spectrum includes AEC syndrome (which subsumes Rapp-Hodgkin syndrome), EEC syndrome type 3, ADULT syndrome, limb-mammary syndrome, and split-hand/foot malformation type 4. The pattern of mutations is distinct for each subtype, with mutations having dominant negative and gain-of-function effects rather than simple loss of function. Approximately 70% of cases arise de novo.
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name: TP63-Related Ectodermal Dysplasia Spectrum
creation_date: "2026-04-04T00:00:00Z"
updated_date: "2026-04-07T14:40:03Z"
description: >-
The TP63-related disorders comprise a spectrum of overlapping autosomal
dominant ectodermal dysplasia syndromes caused by heterozygous mutations in
TP63, which encodes the transcription factor p63. Individuals typically have
varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia,
sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot
malformation or syndactyly, lacrimal duct obstruction, hypopigmentation,
hypoplastic breasts and/or nipples, and hypospadias. The spectrum includes
AEC syndrome (which subsumes Rapp-Hodgkin syndrome), EEC syndrome type 3,
ADULT syndrome, limb-mammary syndrome, and split-hand/foot malformation
type 4. The pattern of mutations is distinct for each subtype, with mutations
having dominant negative and gain-of-function effects rather than simple
loss of function. Approximately 70% of cases arise de novo.
category: Genetic
parents:
- Ectodermal Dysplasia
- Limb Malformation
disease_term:
preferred_term: TP63-related ectodermal dysplasia spectrum
term:
id: MONDO:1040001
label: TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations
has_subtypes:
- name: AEC
display_name: Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC/Hay-Wells) Syndrome
description: >-
Characterized by ankyloblepharon filiforme adnatum, severe skin erosions
especially on the scalp, ectodermal dysplasia, and cleft lip/palate.
Rapp-Hodgkin syndrome is now considered the same entity. Mutations cluster
in the SAM and TI domains (exons 13-14) of the DeltaNp63alpha isoform.
subtype_term:
preferred_term: ankyloblepharon-ectodermal defects-cleft lip/palate syndrome
term:
id: MONDO:0007124
label: ankyloblepharon-ectodermal defects-cleft lip/palate syndrome
- name: EEC3
display_name: Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome Type 3
description: >-
Characterized by ectrodactyly (split hand/foot), ectodermal dysplasia,
and cleft lip/palate. Mutations cluster in the DNA-binding domain of p63.
subtype_term:
preferred_term: ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
term:
id: MONDO:0011428
label: ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
- name: ADULT
display_name: Acro-Dermo-Ungual-Lacrimal-Tooth (ADULT) Syndrome
description: >-
Characterized by ectrodactyly, excessive freckling, lacrimal duct
obstruction, hypodontia, nail dysplasia, hypoplastic breasts, and
sparse hair. Distinguished by prominent freckling and lacrimal
involvement.
subtype_term:
preferred_term: ADULT syndrome
term:
id: MONDO:0007072
label: ADULT syndrome
- name: LMS
display_name: Limb-Mammary Syndrome
description: >-
Characterized by split-hand/foot malformation or other limb
abnormalities, hypoplastic or absent mammary glands and nipples,
and variable ectodermal features.
subtype_term:
preferred_term: limb-mammary syndrome
term:
id: MONDO:0011334
label: limb-mammary syndrome
- name: RHS
display_name: Rapp-Hodgkin Syndrome
description: >-
Now considered the same entity as AEC syndrome. Historically
distinguished by ectodermal dysplasia with cleft lip/palate
but without ankyloblepharon. Mutations overlap with AEC in
the SAM and TI domains.
subtype_term:
preferred_term: Rapp-Hodgkin syndrome
term:
id: MONDO:0007508
label: Rapp-Hodgkin syndrome
prevalence:
- population: Global
percentage: Rare
inheritance:
- name: Autosomal Dominant
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
pathophysiology:
- name: TP63 Mutations and p63 Transcription Factor Dysfunction
description: >-
TP63 encodes p63, a transcription factor critical for ectodermal
development, limb morphogenesis, and orofacial formation. Heterozygous
mutations have both dominant negative and gain-of-function effects on
the p63 protein rather than causing simple loss of function. The pattern
of mutations determines the specific syndrome: DNA-binding domain
mutations cause EEC3, SAM domain mutations cause AEC/Rapp-Hodgkin, and
other domain mutations cause ADULT and limb-mammary syndromes. The
DeltaNp63alpha isoform is particularly critical for the AEC/RHS
phenotype.
genes:
- preferred_term: TP63
term:
id: hgnc:15979
label: TP63
molecular_functions:
- preferred_term: DNA-binding transcription factor activity, RNA polymerase II-specific
term:
id: GO:0000981
label: DNA-binding transcription factor activity, RNA polymerase II-specific
cell_types:
- preferred_term: Keratinocyte
term:
id: CL:0000312
label: keratinocyte
- preferred_term: Epidermal cell
term:
id: CL:0000362
label: epidermal cell
biological_processes:
- preferred_term: Epidermis development
term:
id: GO:0008544
label: epidermis development
- preferred_term: Keratinocyte differentiation
term:
id: GO:0030216
label: keratinocyte differentiation
locations:
- preferred_term: Skin
term:
id: UBERON:0002097
label: skin of body
evidence:
- reference: PMID:12070241
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The pattern of heterozygous mutations is distinct for each of
these syndromes. The functional effects on the p63 proteins also
vary between syndromes.
explanation: >-
Establishes that different TP63 mutation patterns cause distinct
syndromes within the spectrum.
- reference: PMID:12070241
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In all of these syndromes, the mutation appears to have both
dominant negative and gain of function effects rather than causing
a simple loss of function.
explanation: >-
Clarifies that TP63 mutations act through dominant negative/GOF
rather than haploinsufficiency.
- reference: PMID:19676060
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
AEC and RHS mutations in the 5' and 3' ends of the p63 gene
point towards a critical role of the DeltaNp63alpha isoform for
the AEC/RHS phenotype.
explanation: >-
Identifies the DeltaNp63alpha isoform as key to AEC/Rapp-Hodgkin.
downstream:
- target: Ectodermal Dysplasia and Skin Fragility
- target: Limb and Orofacial Malformations
- name: Ectodermal Dysplasia and Skin Fragility
description: >-
Disruption of p63-dependent transcription programs in ectodermal
progenitor cells leads to defective development of skin appendages
(hair, nails, teeth, sweat glands). In AEC syndrome, severe neonatal
skin erosions particularly on the scalp can cause life-threatening
complications including dehydration, electrolyte imbalances, and
infection.
cell_types:
- preferred_term: Keratinocyte
term:
id: CL:0000312
label: keratinocyte
biological_processes:
- preferred_term: Keratinocyte differentiation
term:
id: GO:0030216
label: keratinocyte differentiation
locations:
- preferred_term: Skin
term:
id: UBERON:0002097
label: skin of body
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Skin erosions are treated with gentle wound care and periodic,
dilute bleach soaks to prevent secondary infection, and infants
with severe skin erosions are monitored and treated aggressively
for dehydration, electrolyte imbalances, malnutrition, and
infection.
explanation: >-
GeneReviews describes severe neonatal skin erosions requiring
aggressive management.
- name: Limb and Orofacial Malformations
description: >-
p63 is essential for limb bud development and orofacial morphogenesis.
Dysfunction leads to ectrodactyly (split hand/foot malformation),
syndactyly, cleft lip and/or palate, and other limb anomalies. The
severity and pattern depend on the specific TP63 mutation domain.
biological_processes:
- preferred_term: Limb development
term:
id: GO:0060173
label: limb development
locations:
- preferred_term: Limb
term:
id: UBERON:0002101
label: limb
phenotypes:
- category: Dermatologic
name: Ectodermal Dysplasia
frequency: VERY_FREQUENT
description: >-
Hypohidrosis, nail dysplasia, sparse hair, and tooth abnormalities
are present in varying degrees across all subtypes.
phenotype_term:
preferred_term: Ectodermal dysplasia
term:
id: HP:0000968
label: Ectodermal dysplasia
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Individuals typically have varying combinations of ectodermal
dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth
abnormalities)
explanation: >-
GeneReviews describes ectodermal dysplasia as a core feature.
- category: Craniofacial
name: Cleft Lip and/or Palate
frequency: FREQUENT
description: >-
Orofacial clefting is common across the spectrum, particularly
in AEC and EEC3 subtypes.
phenotype_term:
preferred_term: Cleft lip and/or palate
term:
id: HP:0000202
label: Orofacial cleft
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Individuals typically have varying combinations of ectodermal
dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth
abnormalities), cleft lip/palate, split-hand/foot
malformation/syndactyly, lacrimal duct obstruction,
hypopigmentation, hypoplastic breasts and/or nipples, and
hypospadias.
explanation: >-
GeneReviews lists cleft lip/palate as a core feature of the
TP63-related disorder spectrum.
- category: Musculoskeletal
name: Split Hand/Foot Malformation
frequency: FREQUENT
description: >-
Ectrodactyly (split hand/foot) and syndactyly, most prominent
in EEC3 and ADULT subtypes.
phenotype_term:
preferred_term: Split hand
term:
id: HP:0001171
label: Split hand
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Individuals typically have varying combinations of ectodermal
dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth
abnormalities), cleft lip/palate, split-hand/foot
malformation/syndactyly, lacrimal duct obstruction,
hypopigmentation, hypoplastic breasts and/or nipples, and
hypospadias.
explanation: >-
GeneReviews lists split-hand/foot malformation/syndactyly as a
core feature of the TP63-related disorder spectrum.
- category: Ophthalmologic
name: Ankyloblepharon
frequency: OCCASIONAL
subtype: AEC
description: >-
Ankyloblepharon filiforme adnatum (tissue strands fusing upper and
lower eyelids) is a distinctive finding in AEC syndrome.
phenotype_term:
preferred_term: Ankyloblepharon
term:
id: HP:0009755
label: Ankyloblepharon
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
ankyloblepharon filiforme adnatum (tissue strands that completely
or partially fuse the upper and lower eyelids)
explanation: >-
Ankyloblepharon is specific to the AEC subtype.
- category: Dermatologic
name: Scalp Skin Erosions
frequency: OCCASIONAL
subtype: AEC
description: >-
Skin erosions especially on the scalp. Can be severe and
life-threatening in neonates due to dehydration, electrolyte
imbalances, and infection.
phenotype_term:
preferred_term: Scalp skin erosions
term:
id: HP:0200042
label: Skin ulcer
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
skin erosions especially on the scalp associated with areas of
scarring, and alopecia
explanation: >-
Scalp skin erosions are an AEC-specific feature. HP:0200042
(Skin ulcer) is the closest available HPO term for erosions.
- category: Dermatologic
name: Scarring Alopecia of Scalp
frequency: OCCASIONAL
subtype: AEC
description: >-
Scarring alopecia (cicatricial alopecia) of the scalp, associated
with skin erosions in AEC syndrome.
phenotype_term:
preferred_term: Scarring alopecia of scalp
term:
id: HP:0004552
label: Scarring alopecia of scalp
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
skin erosions especially on the scalp associated with areas of
scarring, and alopecia
explanation: >-
Scarring alopecia is an AEC-specific feature.
- category: Dental
name: Hypodontia
frequency: FREQUENT
description: >-
Reduced number of teeth as part of ectodermal dysplasia.
phenotype_term:
preferred_term: Hypodontia
term:
id: HP:0000668
label: Hypodontia
- category: Dermatologic
name: Nail Dysplasia
frequency: FREQUENT
description: >-
Nail abnormalities including dystrophic or absent nails.
phenotype_term:
preferred_term: Nail dysplasia
term:
id: HP:0002164
label: Nail dysplasia
- category: Dermatologic
name: Hypohidrosis
frequency: FREQUENT
description: >-
Reduced sweating due to sweat gland hypoplasia, part of the
ectodermal dysplasia phenotype.
phenotype_term:
preferred_term: Hypohidrosis
term:
id: HP:0000966
label: Hypohidrosis
- category: Ophthalmologic
name: Lacrimal Duct Obstruction
frequency: OCCASIONAL
description: >-
Lacrimal duct obstruction or atresia, particularly in ADULT
syndrome.
phenotype_term:
preferred_term: Lacrimal duct atresia
term:
id: HP:0000564
label: Lacrimal duct atresia
- category: Breast
name: Breast Hypoplasia
frequency: OCCASIONAL
description: >-
Hypoplastic breasts and/or nipples, particularly in ADULT
and limb-mammary subtypes.
phenotype_term:
preferred_term: Breast hypoplasia
term:
id: HP:0003187
label: Breast hypoplasia
- category: Dermatologic
name: Excessive Freckling
frequency: OCCASIONAL
subtype: ADULT
description: >-
Prominent freckling is a distinctive feature of ADULT syndrome.
phenotype_term:
preferred_term: Freckling
term:
id: HP:0001480
label: Freckling
genetic:
- name: TP63 Heterozygous Mutations
association: Pathogenic Variants
gene_term:
preferred_term: TP63
term:
id: hgnc:15979
label: TP63
inheritance:
- name: Autosomal Dominant
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
features: >-
Heterozygous missense, frameshift, or other mutations with dominant
negative and gain-of-function effects. Mutation pattern correlates
with syndrome subtype: DNA-binding domain (EEC3), SAM/TI domain
(AEC/Rapp-Hodgkin). About 70% de novo, 30% inherited.
evidence:
- reference: PMID:12070241
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Several autosomal dominantly inherited human syndromes have
recently been shown to result from mutations in the p63 gene.
explanation: >-
Establishes TP63 mutations as causative for the syndrome family.
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The proportion of individuals with a TP63-related disorder caused
by a de novo TP63 pathogenic variant is approximately 70%.
explanation: >-
GeneReviews confirms high de novo rate.
- reference: PMID:19676060
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Eight were missense mutations within the coding region of the SAM
domain. Three other mutations were located in exon 14 sequences,
which encode the TI domain.
explanation: >-
Characterizes mutation clustering in SAM/TI domains for AEC/RHS.
treatments:
- name: Multidisciplinary Care
description: >-
A multidisciplinary team including genetics, dermatology,
ophthalmology, otolaryngology, audiology, dentistry, plastic
surgery, and nutrition is recommended.
treatment_term:
preferred_term: Multidisciplinary care
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A multidisciplinary team of specialists in clinical genetics,
dermatology, ophthalmology, otolaryngology, audiology, dentistry
and prosthodontics, plastic surgery, nutrition/gastroenterology,
and psychology is recommended.
explanation: >-
GeneReviews management guidance.
- name: Wound Care for Skin Erosions
description: >-
Gentle wound care with dilute bleach soaks to prevent secondary
infection. Aggressive monitoring for dehydration, electrolyte
imbalances, and malnutrition in severe neonatal cases.
treatment_term:
preferred_term: Wound care
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Skin erosions are treated with gentle wound care and periodic,
dilute bleach soaks to prevent secondary infection
explanation: >-
GeneReviews skin erosion management.
- name: Cleft Lip/Palate Repair
description: >-
Surgical repair of cleft lip and/or palate per routine protocols.
treatment_term:
preferred_term: Cleft repair surgery
term:
id: MAXO:0000004
label: surgical procedure
- name: Dental Rehabilitation
description: >-
Dentures in early childhood, dental implants in teens or early
adulthood for hypodontia.
treatment_term:
preferred_term: Dental rehabilitation
term:
id: MAXO:0000950
label: supportive care
- name: Genetic Counseling
description: >-
Genetic counseling regarding autosomal dominant inheritance with
70% de novo rate. Prenatal and preimplantation genetic testing
available once the family variant is identified.
treatment_term:
preferred_term: Genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
evidence:
- reference: PMID:20556892
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Once the TP63 pathogenic variant has been identified in an
affected family member, prenatal and preimplantation genetic
testing are possible.
explanation: >-
GeneReviews genetic counseling guidance.
notes: >-
Split-hand/foot malformation type 4 (SHFM4) is part of the TP63-related
disorder spectrum per GeneReviews but was not included in the G2P priority
curation list. It is caused by TP63 mutations and presents primarily with
isolated ectrodactyly without significant ectodermal dysplasia features.
Isolated orofacial cleft 8 is also in the spectrum.
datasets:
references:
- reference: PMID:20556892
title: "TP63-Related Disorders."
tags:
- GeneReviews
findings: []
TP63-related ectodermal dysplasia spectrum comprises multiple autosomal-dominant developmental syndromes caused by heterozygous pathogenic variants in TP63 (p63), a p53-family transcription factor essential for epithelial development and stem cell maintenance. The spectrum includes at least EEC, AEC (Hay–Wells), ADULT, limb–mammary syndrome, Rapp–Hodgkin syndrome, and split-hand/foot malformation 4 (SHFM4), with significant genotype–phenotype correlation by protein domain (DBD/OD vs SAM/TI) and allele-specific mechanisms (dominant-negative, gain-of-function, aggregation, isoform imbalance). Recent 2023–2024 work expands clinically actionable domains: (i) iPSC and in vivo models in AEC link hemidesmosome/focal-adhesion downregulation to skin erosions, (ii) rare neonatal T-cell lymphopenia/athymia presentations detected by newborn TREC screening with WES/WGS and treated with cultured thymus tissue implant, and (iii) a large 2023 cohort shows TP63 gain-of-function variants contribute ~0.78% of idiopathic primary ovarian insufficiency cases via constitutive TAp63α tetramerization and oocyte apoptosis. (salois2023effectsoftp63 pages 3-4, gall2024casereportartificial pages 2-3, huang2023tp63gainoffunctionmutations pages 2-3)
| Entity | Common synonym / expansion | OMIM / MIM noted in provided texts | Orphanet prevalence note in provided texts | Key TP63 domain(s) typically involved in provided texts | Notes / scope | Citations |
|---|---|---|---|---|---|---|
| TP63-related ectodermal dysplasia spectrum | TP63-related disorders; p63-associated disorders; TP63-associated syndromes | TP63 gene: MIM 603273 | Prenatal WES paper states the spectrum comprises six autosomal dominant syndromes | Predominantly DNA-binding domain (DBD) and sterile alpha motif (SAM); review notes ~80% of pathogenic changes affect DBD/OD, while AEC is strongly linked to SAM-domain lesions | Umbrella concept including EEC, AEC/Hay-Wells, Rapp-Hodgkin, ADULT, limb-mammary syndrome, and split-hand/foot malformation 4 | (cong2026p63inskin pages 12-14, gall2024casereportartificial pages 2-3) |
| EEC syndrome | Ectrodactyly-ectodermal dysplasia-clefting; ectrodactyly-ectodermal dysplasia-cleft lip/palate | ~1–9 per 100,000 newborns (Orpha.net, as quoted in 2023 ocular series) | DBD hotspot residues repeatedly noted (R204, R227, R279, R280, R304; also examples R279C/R279H/R340G) | Core triad is limb malformation, ectodermal dysplasia, and cleft lip/palate; important ocular morbidity includes limbal stem cell deficiency | (iorio2023…patientsaffected pages 9-11, cong2026p63inskin pages 12-14) | |
| AEC syndrome | Ankyloblepharon-ectodermal defects-cleft lip/palate; Ankyloblepharon-ectodermal dysplasia-clefting; Hay-Wells syndrome | SAM domain mutations emphasized; example p.Gly600Val in exon 14; aggregation/misfolding mechanism also highlighted in review literature | Distinguished by ankyloblepharon and severe skin erosions/erythroderma with ectodermal defects and clefting | (cong2026p63inskin pages 12-14, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 4-4) | ||
| Rapp-Hodgkin syndrome | RHS | Reported within TP63 SAM/other ectodermal-dysplasia-associated domains; 2026 review lists examples including 1709DelA and R279H | Historically considered overlapping with AEC; provided texts describe RHS as resembling AEC with mid-facial hypoplasia and no ankyloblepharon | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, cong2026p63inskin pages 14-16) | ||
| ADULT syndrome | Acro-dermato-ungual-lacrimal-tooth syndrome | Commonly DBD-associated in provided texts; recurrent residues listed include R298Q, R298G, R243W, R227Q; 2026 review highlights R298 and Q243W | Often includes lacrimal duct anomalies, nail/tooth defects, sparse hair, and mammary hypoplasia; freckling may help distinguish from EEC/AEC | (zhou2023casereportadult pages 2-4, cong2026p63inskin pages 14-16) | ||
| Limb-mammary syndrome | LMS | MIM #603543 (noted in provided text) | Mutations reported in provided review include R204Q and R227Q (DBD-associated examples) | Characterized by limb defects and mammary/nipple hypoplasia; cleft palate may occur with relatively limited skin involvement | (zhou2023casereportadult pages 2-4, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4) | |
| Split-hand/foot malformation 4 | SHFM4 | Usually DBD-associated in the provided mechanistic literature; p.Arg319His and p.Met307Ile are examples discussed in recent/foundational reports | May occur as isolated limb malformation or overlap with broader TP63 syndromes; incomplete penetrance reported | (zhuang2025molecularcharacterizationof pages 9-10, gall2024casereportartificial pages 2-3) |
Table: This table summarizes the umbrella TP63-related ectodermal dysplasia concept and the major named syndromes included in the spectrum. It highlights synonyms, any OMIM/MIM or prevalence details explicitly available in the retrieved texts, and the TP63 protein domains most often implicated.
TP63-related ectodermal dysplasia spectrum is an umbrella term for clinically overlapping developmental syndromes caused by germline TP63 variants, characterized by variable combinations of: - ectodermal defects (skin, hair, nails, teeth, sweat glands), - craniofacial anomalies (cleft lip/palate), - limb malformations (ectrodactyly/split-hand-foot), - and, in some individuals, severe ocular surface disease (limbal stem cell deficiency) and rarer immune or gonadal phenotypes. (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, iorio2023…patientsaffected pages 9-11, gall2024casereportartificial pages 2-3)
Not found in retrieved documents: MONDO ID, MeSH ID, ICD-10/ICD-11 codes.
The present synthesis draws on: - Human clinical reports/series (2023–2024): ocular EEC/AEC series and multiple case reports including lacrimal surgery and newborn immunology presentations (iorio2023…patientsaffected pages 9-11, zhou2023casereportadult pages 2-4, gall2024casereportartificial pages 2-3) - Human genetics cohort study (2023): TP63 gain-of-function variants in primary ovarian insufficiency (huang2023tp63gainoffunctionmutations pages 2-3) - Mechanistic experimental study (2023): iPSC-derived keratinocytes, gene-corrected lines, and in vivo validation in mice for AEC skin erosions (salois2023effectsoftp63 pages 3-4) - Review synthesis (2025–2026): domain/genotype correlations and isoform biology used as contextual “expert consensus” sources (cong2026p63inskin pages 12-14, murari2025p63amaster pages 4-6)
No protective genetic or environmental factors were identified in the retrieved texts.
No direct GxE evidence was identified in the retrieved texts.
Major phenotype groupings, onset patterns, and relevant HPO mappings are summarized below.
| Clinical feature | Suggested HPO term(s) | Typical syndromes | Onset/course notes | Evidence |
|---|---|---|---|---|
| Ectrodactyly / split-hand-foot malformation | Ectrodactyly (HP:0100259); Split hand (HP:0001171); Split foot (HP:0001839) | EEC, SHFM4, sometimes ADULT/LMS overlap | Congenital limb malformation; may occur in isolation (SHFM4) or with broader ectodermal findings; incomplete penetrance reported for SHFM4 | (zhuang2025molecularcharacterizationof pages 9-10, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Cleft lip and/or palate / high-arched palate | Cleft upper lip (HP:0000204); Cleft palate (HP:0000175); High palate / High-arched palate (HP:0000218) | EEC, AEC, LMS; high-arched palate reported in AEC/ADULT cases | Congenital craniofacial anomaly; clefting is part of classic EEC triad, while LMS may show cleft palate without extensive skin disease | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 4-4) |
| Skin erosions / fragile skin / xerosis | Skin erosion (HP:0008066); Xerosis (HP:0001024); Fragile skin | AEC, EEC | Usually neonatal/early childhood in AEC; may be chronic, recurrent, and wound-healing related; fragile/xerotic skin also described in EEC | (cong2026p63inskin pages 12-14, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, salois2023effectsoftp63 pages 3-4, salois2023effectsoftp63 pages 4-6) |
| Sparse hair / hypotrichosis | Hypotrichosis (HP:0001006); Sparse scalp hair (HP:0008070) | EEC, AEC, ADULT | Congenital or early-childhood ectodermal manifestation; generally chronic/non-progressive though severity varies | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Nail dystrophy / onychodystrophy | Nail dysplasia (HP:0002164); Onychodystrophy | EEC, AEC, ADULT, LMS | Congenital/childhood onset; persistent structural nail abnormality | (cong2026p63inskin pages 12-14, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Hypodontia / oligodontia / conical teeth | Hypodontia (HP:0009804); Oligodontia (HP:0000677); Conical tooth/teeth (HP:0000698) | EEC, AEC, ADULT | Usually recognized in childhood with tooth eruption failure/abnormal morphology; important functional and QoL impact on feeding, speech, dentition | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Hypohidrosis | Hypohidrosis (HP:0000975) | AEC, ADULT, broader TP63-ED spectrum | Present from infancy/childhood; chronic reduced sweating may affect heat tolerance | (zhou2023casereportadult pages 2-4, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 4-4) |
| Lacrimal duct anomalies / epiphora | Nasolacrimal duct obstruction; Lacrimal duct aplasia/atresia; Epiphora (HP:0001132) | ADULT, EEC | Congenital lacrimal outflow abnormality; may present with chronic tearing and require surgical correction | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Ankyloblepharon / symblepharon | Ankyloblepharon (HP:0000627); Symblepharon | AEC, ADULT overlap, EEC ocular disease spectrum | Congenital eyelid fusion in AEC; symblepharon may complicate chronic ocular surface disease | (cong2026p63inskin pages 12-14, iorio2023…patientsaffected pages 9-11, zhou2023casereportadult pages 2-4) |
| Limbal stem cell deficiency / corneal neovascularization / pannus | Limbal stem cell deficiency; Corneal neovascularization (HP:0007710); Corneal pannus | EEC, broader TP63 ocular spectrum | Progressive ocular surface disease causing corneal thinning, conjunctivalization, neovascularization, pannus, and vision loss | (iorio2023…patientsaffected pages 9-11, iorio2023…patientsaffected pages 14-14) |
| Meibomian gland agenesis / dysfunction | Meibomian gland abnormality; Meibomian gland aplasia/agenesis | EEC, ADULT ocular involvement | Congenital adnexal abnormality contributing to tear-film instability and ocular surface desiccation | (iorio2023…patientsaffected pages 9-11, iorio2023…patientsaffected pages 14-14) |
| T-cell lymphopenia / athymia | T cell lymphopenia (HP:0005403); Athymia / Thymic hypoplasia | Overlapping TP63-related syndrome (EEC/AEC-like presentations) | Detected in newborn period by low/undetectable TREC; may reflect thymic stromal/epithelial defect and can be severe/persistent | (gall2024casereportartificial pages 2-3, marakhonov2024ararecase pages 1-2, marakhonov2024ararecase pages 10-10) |
| Mammary gland hypoplasia / absent nipples or breasts | Breast hypoplasia (HP:0000769); Nipple hypoplasia / Athelia | ADULT, LMS | Congenital developmental anomaly; often useful for syndrome differentiation from EEC/AEC | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4) |
| Primary ovarian insufficiency | Primary ovarian insufficiency (HP:0008209); Hypergonadotropic hypogonadism | TP63-related ovarian phenotype; may overlap with LMS or occur in isolated TP63-associated disease | Usually adolescent/adult presentation with amenorrhea/infertility; mechanistically linked to constitutive TAp63 activation and oocyte apoptosis | (цабаи2025нарушенияполовогоразвития pages 10-10, vanderschelden2023heterozygoustp63pathogenic pages 1-2) |
Table: This table maps clinically important features reported across the TP63-related ectodermal dysplasia spectrum to suggested HPO terms, typical syndrome associations, and brief onset/course notes. It is useful as a structured phenotype curation aid for knowledge-base entry and differential diagnosis.
Key clinically prominent phenotypes supported by 2023–2024 evidence include: - Progressive ocular surface disease in EEC: progressive limbal stem cell deficiency (LSCD) is described as the most disabling manifestation in most patients, leading to corneal thinning, neovascularization, pannus, conjunctivalization, and gradual vision loss/blindness, compounded by meibomian gland agenesis and tear-film instability (human clinical series) (iorio2023…patientsaffected pages 9-11). - AEC skin erosions: extensive skin erosions/fragility in AEC with molecularly defined adhesion defects (see Mechanisms) (salois2023effectsoftp63 pages 3-4). - Congenital lacrimal abnormalities in ADULT: lacrimal duct aplasia/stenosis with chronic epiphora, treated surgically (zhou2023casereportadult pages 2-4). - Rare immune phenotype: newborn-detected profound T-cell lymphopenia and suspected congenital athymia in TP63-related syndrome (gall2024casereportartificial pages 2-3). - Gonadal phenotype: isolated primary ovarian insufficiency due to TP63 gain-of-function variants (huang2023tp63gainoffunctionmutations pages 2-3).
Quality-of-life impact is most explicitly documented for ocular disease (severe photophobia, marked vision impairment, multiple surgeries, and reports of total ocular surface impairment) (iorio2023…patientsaffected pages 9-11).
No explicit modifier genes or disease-specific epigenetic signatures were identified in the retrieved evidence set.
No non-genetic environmental contributors were identified in the retrieved evidence set; TP63 disorders are primarily monogenic developmental disorders.
TP63 encodes multiple isoforms; ΔNp63 is central to epithelial stemness and keratinocyte programs, whereas TAp63α plays a critical role in oocyte quality control and apoptosis. Isoform imbalance can alter keratinocyte fate decisions (cong2026p63inskin pages 12-14, murari2025p63amaster pages 4-6).
Human iPSC + in vivo validation demonstrate that AEC-associated TP63 SAM-domain mutations can drive a coordinated reduction of hemidesmosome and focal-adhesion programs: - Salois et al. (Experimental Dermatology, 2023-07; https://doi.org/10.1111/exd.14885) used patient-derived iPSC lines (AEC mutations F513S, I537T, R598L), created gene-corrected isogenic controls, and differentiated both into keratinocytes. They identified downregulation of hemidesmosome components such as ITGA6, ITGB4, COL17A1, cytoplasmic adaptors DST, PLEC, and laminin-332 genes LAMA3, LAMB3, LAMC2, with impaired keratinocyte adhesion and migration across ECM substrates. They propose integrin defects weaken keratinocyte anchorage to basement membrane and contribute to erosions (salois2023effectsoftp63 pages 3-4, salois2023effectsoftp63 pages 4-6). - These changes were corroborated in chimeric mice expressing TP63-AEC transgene and in AEC patient skin (salois2023effectsoftp63 pages 3-4, salois2023effectsoftp63 pages 7-11).
Visual evidence: figures summarizing downregulation and schematic model are available from the paper (salois2023effectsoftp63 media 83f76dc6, salois2023effectsoftp63 media e89fc6fc).
Suggested ontology terms: - GO biological process: cell adhesion; epithelial cell migration; extracellular matrix organization; hemidesmosome assembly (supported mechanistically) (salois2023effectsoftp63 pages 3-4). - GO cellular component: hemidesmosome; focal adhesion; basement membrane (salois2023effectsoftp63 pages 3-4). - CL cell types: keratinocyte; epidermal basal cell (ΔNp63-high) (cong2026p63inskin pages 12-14, salois2023effectsoftp63 pages 3-4).
Mechanistic evidence links TP63 to apical ectodermal ridge (AER) programs and downstream transcription factors: - SHFM4 p.Arg319His is hypothesized to disrupt the p63–DLX signaling pathway; DLX5 is a downstream gene altered in patient RNA-seq/qPCR (zhuang2025molecularcharacterizationof pages 1-2). - The same study contextualizes prior work that p63 regulates AER targets and that p63 loss reduces FGF8 causing limb defects (zhuang2025molecularcharacterizationof pages 6-8).
Suggested GO/CL terms: - GO BP: limb development; regulation of transcription involved in pattern specification. - CL: ectodermal cell; limb bud epithelial cell.
Suggested terms: - CL: thymic epithelial cell; T cell. - GO BP: thymus development; T cell differentiation.
Suggested terms: - GO BP: intrinsic apoptotic signaling pathway; oocyte development. - CL: oocyte.
Primary structures (with UBERON suggestions): - Skin / epidermis (UBERON:0002097) and basement membrane zone (supported by hemidesmosome defects) (salois2023effectsoftp63 pages 3-4) - Hair follicles and nails (ectodermal appendages) (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4) - Teeth (tooth development defects: hypodontia/oligodontia) (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4) - Limb autopod (split-hand/foot; ectrodactyly) (zhuang2025molecularcharacterizationof pages 1-2) - Eye / cornea / limbus / meibomian glands / lacrimal system (progressive ocular surface disease; lacrimal duct anomalies) (iorio2023…patientsaffected pages 9-11, zhou2023casereportadult pages 2-4) - Thymus (suspected congenital athymia; thymic epithelial involvement) (gall2024casereportartificial pages 2-3) - Ovary / oocytes (POI due to TAp63α GOF variants) (huang2023tp63gainoffunctionmutations pages 2-3)
Subcellular/localization themes: - Nucleus (transcription factor), chromatin/enhancers (p63 pioneer activity) (cong2026p63inskin pages 16-19) - Cell–matrix junctions: hemidesmosomes, focal adhesions (salois2023effectsoftp63 pages 3-4)
Key clinical patterns: - EEC: ectrodactyly + ectodermal signs + clefting; high risk of ocular surface disease (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, iorio2023…patientsaffected pages 9-11). - AEC: ankyloblepharon and skin erosions prominent (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, ahuja2023ectrodactylyectodermaldysplasiaclefting pages 4-4). - ADULT: lacrimal anomalies and mammary hypoplasia; typically no clefting (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4).
TP63 syndromes overlap; helpful differentiators described in clinical sources include: - AEC: ankyloblepharon + skin erosions, - ADULT: mammary/nipple hypoplasia and freckling with lacrimal disease and typically absent clefting, - LMS: limb + mammary defects with limited skin involvement, - EEC: classic triad and high ocular morbidity. (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 2-4, zhou2023casereportadult pages 2-4)
See intervention mapping table:
| Domain / variant type | Example variants (from evidence) | Proposed mechanism | Associated phenotype / syndrome | Diagnostic approach used | Real-world intervention with suggested MAXO term name(s) | Evidence citations |
|---|---|---|---|---|---|---|
| DNA-binding domain missense hotspot | p.Arg279Cys, p.Arg279His, p.Arg340Gly | Reported as impairing p63 function; ocular series describes heterozygous missense mutations causing haploinsufficiency in tetrameric p63 complexes, with progressive limbal stem-cell deficiency as a major downstream consequence | EEC with severe ocular disease, including LSCD, corneal thinning/neovascularization, pannus, vision loss | Clinical phenotyping plus TP63 variant detection in affected patients | Ocular surface surveillance and reconstructive procedures reported in case series, including corneal transplantation / amniotic grafting; suggested MAXO: ophthalmologic examination, corneal transplantation, amniotic membrane transplantation | (iorio2023…patientsaffected pages 9-11, iorio2023…patientsaffected pages 14-14) |
| DNA-binding domain missense, de novo | p.Arg343Trp (c.1027C>T) | Reduced TP63 transactivation in a dominant-negative manner; structural modeling suggests loss of DNA-contact and destabilization | EEC3 / TP63-associated syndrome with neonatal T-cell lymphopenia | Newborn TREC screening followed by confirmatory immunophenotyping and WES | Comprehensive immunologic evaluation and longitudinal immune monitoring; suggested MAXO: immunologic monitoring, newborn screening, exome sequencing | (marakhonov2024ararecase pages 1-2, marakhonov2024ararecase pages 4-5) |
| DNA-binding domain missense, de novo | p.Cys347Tyr (c.1040G>A) | Thymic stromal / epithelial defect suspected rather than hematopoietic-intrinsic failure; TP63 expression restricted to thymic epithelial cells in referenced analysis | Overlapping TP63-related syndrome with profound neonatal T-cell lymphopenia / suspected congenital athymia | Undetectable TREC on newborn screen, flow cytometry, rapid WGS, artificial thymic organoid assay | Allogeneic cultured thymus tissue implant; suggested MAXO: thymus tissue transplantation, flow cytometry, genome sequencing | (gall2024casereportartificial pages 2-3) |
| SAM-domain missense | p.F513S, p.I537T, p.R598L | AEC-associated reduction of hemidesmosome/focal-adhesion components; impaired keratinocyte adhesion and migration; review literature also describes SAM mutations as causing pathological aggregation / functional loss | AEC (Hay-Wells) with skin erosions / fragility | Patient-derived iPSC generation, genome editing to create gene-corrected controls, RNA-seq, qRT-PCR, Western blot, validation in chimeric mice and patient skin | Supportive wound/skin care is implied standard care; experimental mechanism-guided approaches under development; suggested MAXO: wound care, skin barrier therapy, induced pluripotent stem cell assay | (salois2023effectsoftp63 pages 3-4, salois2023effectsoftp63 pages 1-3, salois2023effectsoftp63 pages 4-6, salois2023effectsoftp63 pages 7-11, cong2026p63inskin pages 12-14) |
| SAM-domain missense, de novo | p.Gly600Val (c.1799G>T) | Molecular modeling suggests local conformational distortion affecting protein-protein interactions | AEC with extensive skin erosions, erythroderma, nail dystrophy, xerophthalmia, oligodontia, hypohidrosis | Clinical evaluation plus TP63 sequencing and protein structural modeling | Symptomatic multidisciplinary care for skin, eye, dental, and craniofacial disease; suggested MAXO: dermatologic care, dental care, ophthalmologic care, cleft repair | (ahuja2023ectrodactylyectodermaldysplasiaclefting pages 4-4) |
| DNA-binding domain missense associated with ADULT | p.G173V (c.518G>T); recurrent ADULT residues listed include R298Q, R298G, R243W, R227Q, P127L, R337Q, V114M, N6H | Variant predicted deleterious; ADULT literature/reviews support gain-of-function transactivation for some ADULT alleles | ADULT syndrome with lacrimal duct aplasia/stenosis, symblepharon, sparse hair, nail dystrophy, oligodontia, mammary hypoplasia, digit anomalies | WES with Sanger confirmation | Binocular dacryocystorhinostomy with artificial tear duct implantation and duct excision; suggested MAXO: dacryocystorhinostomy, lacrimal duct stent placement, ophthalmologic surgery | (zhou2023casereportadult pages 2-4, murari2025p63amaster pages 4-6) |
| DNA-binding domain missense with incomplete penetrance | p.Arg319His (c.956G>A); related residue p.Arg319Cys | Family study proposes gain-of-function effect with upregulation of TP63 downstream genes (CDH3, DLX5), disrupting p63-DLX/AER biology; explicit incomplete penetrance and variable expressivity | SHFM4 with isolated limb malformations in some carriers and unaffected carriers in same family | WES, RNA-seq, qPCR, structural modeling, ACMG classification, exclusion of chromosomal abnormalities by karyotype/CMA | Genetic counseling and prenatal diagnosis relevance emphasized; suggested MAXO: genetic counseling, prenatal genetic testing, exome sequencing | (zhuang2025molecularcharacterizationof pages 1-2, zhuang2025molecularcharacterizationof pages 6-8, zhuang2025molecularcharacterizationof pages 4-6) |
| TAp63α C-terminal / transactivation inhibitory domain-disrupting variants | p.R647C and other TID-disrupting heterozygous mutations; truncating variants and intragenic CNV affecting TP63 also reported | Isoform-specific constitutive activation of TAp63α tetramers, driving oocyte apoptosis; loss of inactive dimeric conformation | Isolated primary ovarian insufficiency / hypergonadotropic hypogonadism; occasionally overlap with limb-mammary phenotypes | WES with CNV confirmation by long-range PCR and Sanger; cohort screening in POI patients | Reproductive / endocrine management and genetic counseling are the practical applications described; suggested MAXO: genetic counseling, fertility counseling, endocrine evaluation | (vanderschelden2023heterozygoustp63pathogenic pages 1-2, цабаи2025нарушенияполовогоразвития pages 10-10, murari2025p63amaster pages 4-6) |
| Mixed TP63 ectodermal dysplasia spectrum, mostly DBD or OD lesions | DBD hotspots R204, R227, R279, R280, R304; LMS examples R204Q, R227Q; ADULT examples R298/Q243W | Broadly loss-of-function, gain-of-function, isoform imbalance, and domain-specific aggregation mechanisms; ~80% of pathogenic mutations cluster in DBD/OD per review synthesis | EEC, AEC, ADULT, LMS, RHS, SHFM4 | Syndrome-directed molecular testing, panel/exome/genome sequencing depending presentation | Current care mainly supportive and surgical; emerging strategies include allele-specific siRNA, AAV-CRISPR/base editing, limbal stem-cell therapy, and small-molecule disaggregation approaches; suggested MAXO: supportive care, surgery, RNA interference therapy, gene editing therapy, stem cell therapy | (cong2026p63inskin pages 12-14, cong2026p63inskin pages 14-16, murari2025p63amaster pages 2-4) |
Table: This table links TP63 variant classes and domain-specific mechanisms to the main syndromic phenotypes, diagnostic workflows, and real-world interventions reported across the TP63-related ectodermal dysplasia spectrum. It is useful for connecting molecular interpretation to practical disease management.
No primary prevention exists for germline TP63 disorders; prevention focuses on: - Genetic counseling and discussion of recurrence risk, especially given variable expressivity/incomplete penetrance (zhuang2025molecularcharacterizationof pages 1-2). - Prenatal diagnosis is implicated as relevant in TP63 disorders (noted in reference discussion) (iorio2023…patientsaffected pages 14-14). - Secondary prevention through early detection of high-morbidity complications (ocular surveillance; newborn immune screening when applicable) (iorio2023…patientsaffected pages 9-11, gall2024casereportartificial pages 2-3).
No naturally occurring non-human TP63 ectodermal dysplasia disease models or veterinary reports were identified in the retrieved evidence set.
Key model systems and their relevance: - AEC skin fragility models (2023): patient iPSC-derived keratinocytes with gene-corrected controls; chimeric mice expressing TP63-AEC transgene; recapitulate adhesion defects implicated in erosions (salois2023effectsoftp63 pages 3-4, salois2023effectsoftp63 pages 7-11). - POI models (2023): p63+/ΔTID and p63+/R647C mice show rapid postnatal oocyte depletion/POI-like phenotype, supporting gain-of-function mechanism in oocytes (huang2023tp63gainoffunctionmutations pages 3-5, huang2023tp63gainoffunctionmutations pages 5-7). - Developmental limb model context: p63−/− mice associated with reduced AER FGF signaling and limb defects (cited mechanistic context) (zhuang2025molecularcharacterizationof pages 6-8). - Ex vivo functional assay model (2024): artificial thymic organoid assay to separate hematopoietic vs thymic stromal causes of T-cell lymphopenia (gall2024casereportartificial pages 2-3).
References
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(salois2023effectsoftp63 pages 4-6): Maddison N. Salois, Jessica A. Gugger, Saiphone Webb, Christina E. Sheldon, Shirley P. Parraga, G. Michael Lewitt, Dorothy K. Grange, Peter J. Koch, and Maranke I. Koster. Effects of tp63 mutations on keratinocyte adhesion and migration. Experimental Dermatology, 32:1575-1581, Jul 2023. URL: https://doi.org/10.1111/exd.14885, doi:10.1111/exd.14885. This article has 5 citations and is from a domain leading peer-reviewed journal.
(iorio2023…patientsaffected pages 14-14): E Di Iorio, F Bonelli, and R Bievel-Radulescu. … patients affected by p63-associated disorders: ectrodactyly-ectodermal dysplasia-clefting (eec) and ankyloblepharon-ectodermal defects-cleft lip palate (aec …. Unknown journal, 2023.
(marakhonov2024ararecase pages 1-2): Andrey Marakhonov, Elena Serebryakova, Anna Mukhina, Anastasia Vechkasova, Nikolai Prokhorov, Irina Efimova, Natalia Balinova, Anastasia Lobenskaya, Tatyana Vasilyeva, Victoria Zabnenkova, Oxana Ryzhkova, Yulia Rodina, Dmitry Pershin, Nadezhda Soloveva, Anna Fomenko, Djamila Saydaeva, Aset Ibisheva, Taisiya Irbaieva, Alexander Koroteev, Rena Zinchenko, Sergey Voronin, Anna Shcherbina, and Sergey Kutsev. A rare case of tp63-associated lymphopenia revealed by newborn screening using trec. International Journal of Molecular Sciences, 25:10844, Oct 2024. URL: https://doi.org/10.3390/ijms251910844, doi:10.3390/ijms251910844. This article has 4 citations.
(marakhonov2024ararecase pages 10-10): Andrey Marakhonov, Elena Serebryakova, Anna Mukhina, Anastasia Vechkasova, Nikolai Prokhorov, Irina Efimova, Natalia Balinova, Anastasia Lobenskaya, Tatyana Vasilyeva, Victoria Zabnenkova, Oxana Ryzhkova, Yulia Rodina, Dmitry Pershin, Nadezhda Soloveva, Anna Fomenko, Djamila Saydaeva, Aset Ibisheva, Taisiya Irbaieva, Alexander Koroteev, Rena Zinchenko, Sergey Voronin, Anna Shcherbina, and Sergey Kutsev. A rare case of tp63-associated lymphopenia revealed by newborn screening using trec. International Journal of Molecular Sciences, 25:10844, Oct 2024. URL: https://doi.org/10.3390/ijms251910844, doi:10.3390/ijms251910844. This article has 4 citations.
(cong2026p63inskin pages 16-19): Yujia Cong, Zhenglin He, Hanming Hao, Haoran Chen, Anqi Chen, Chunyi Li, Yue Hu, and Xianling Cong. P63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials. Cell Death Discovery, Mar 2026. URL: https://doi.org/10.1038/s41420-026-03060-8, doi:10.1038/s41420-026-03060-8. This article has 0 citations and is from a peer-reviewed journal.
(zhuang2025molecularcharacterizationof pages 6-8): Jianlong Zhuang, Yanqing Li, Yu’e Chen, Hegan Zhang, Shufen Liu, Manman Hu, and Chunnuan Chen. Molecular characterization of a rare tp63 variant associated with split-hand/split-foot malformation 4 and incomplete penetrance: disruption of the p63-dlx signaling pathway. BMC Genomics, Feb 2025. URL: https://doi.org/10.1186/s12864-025-11297-3, doi:10.1186/s12864-025-11297-3. This article has 0 citations and is from a peer-reviewed journal.
(salois2023effectsoftp63 pages 7-11): Maddison N. Salois, Jessica A. Gugger, Saiphone Webb, Christina E. Sheldon, Shirley P. Parraga, G. Michael Lewitt, Dorothy K. Grange, Peter J. Koch, and Maranke I. Koster. Effects of tp63 mutations on keratinocyte adhesion and migration. Experimental Dermatology, 32:1575-1581, Jul 2023. URL: https://doi.org/10.1111/exd.14885, doi:10.1111/exd.14885. This article has 5 citations and is from a domain leading peer-reviewed journal.
(salois2023effectsoftp63 media 83f76dc6): Maddison N. Salois, Jessica A. Gugger, Saiphone Webb, Christina E. Sheldon, Shirley P. Parraga, G. Michael Lewitt, Dorothy K. Grange, Peter J. Koch, and Maranke I. Koster. Effects of tp63 mutations on keratinocyte adhesion and migration. Experimental Dermatology, 32:1575-1581, Jul 2023. URL: https://doi.org/10.1111/exd.14885, doi:10.1111/exd.14885. This article has 5 citations and is from a domain leading peer-reviewed journal.
(salois2023effectsoftp63 media e89fc6fc): Maddison N. Salois, Jessica A. Gugger, Saiphone Webb, Christina E. Sheldon, Shirley P. Parraga, G. Michael Lewitt, Dorothy K. Grange, Peter J. Koch, and Maranke I. Koster. Effects of tp63 mutations on keratinocyte adhesion and migration. Experimental Dermatology, 32:1575-1581, Jul 2023. URL: https://doi.org/10.1111/exd.14885, doi:10.1111/exd.14885. This article has 5 citations and is from a domain leading peer-reviewed journal.
(huang2023tp63gainoffunctionmutations pages 3-5): Chengzi Huang, Simin Zhao, Yajuan Yang, T. Guo, Hanni Ke, Xinling Mi, Yingying Qin, Zi-Jiang Chen, and Shidou Zhao. Tp63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis. The Journal of Clinical Investigation, Mar 2023. URL: https://doi.org/10.1172/jci162315, doi:10.1172/jci162315. This article has 38 citations.
(iorio2023…byp63associated pages 9-11): E Di Iorio, F Bonelli, and R Bievel-Radulescu. … by p63-associated disorders: ectrodactyly-ectodermal dysplasia-clefting (eec) and ankyloblepharon-ectodermal defects-cleft lip palate (aec) syndromes. Unknown journal, 2023.
(huang2023tp63gainoffunctionmutations pages 10-11): Chengzi Huang, Simin Zhao, Yajuan Yang, T. Guo, Hanni Ke, Xinling Mi, Yingying Qin, Zi-Jiang Chen, and Shidou Zhao. Tp63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis. The Journal of Clinical Investigation, Mar 2023. URL: https://doi.org/10.1172/jci162315, doi:10.1172/jci162315. This article has 38 citations.
(salois2023effectsoftp63 pages 1-3): Maddison N. Salois, Jessica A. Gugger, Saiphone Webb, Christina E. Sheldon, Shirley P. Parraga, G. Michael Lewitt, Dorothy K. Grange, Peter J. Koch, and Maranke I. Koster. Effects of tp63 mutations on keratinocyte adhesion and migration. Experimental Dermatology, 32:1575-1581, Jul 2023. URL: https://doi.org/10.1111/exd.14885, doi:10.1111/exd.14885. This article has 5 citations and is from a domain leading peer-reviewed journal.
(murari2025p63amaster pages 2-4): Lakshana Sruthi Sadu Murari, Sam Kunkel, Anala Shetty, Addison Bents, Aayush Bhandary, and Juan Carlos Rivera-Mulia. P63: a master regulator at the crossroads between development, senescence, aging, and cancer. Cells, 14:43, Jan 2025. URL: https://doi.org/10.3390/cells14010043, doi:10.3390/cells14010043. This article has 5 citations.
(huang2023tp63gainoffunctionmutations pages 5-7): Chengzi Huang, Simin Zhao, Yajuan Yang, T. Guo, Hanni Ke, Xinling Mi, Yingying Qin, Zi-Jiang Chen, and Shidou Zhao. Tp63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis. The Journal of Clinical Investigation, Mar 2023. URL: https://doi.org/10.1172/jci162315, doi:10.1172/jci162315. This article has 38 citations.