North Carolina macular dystrophy (NCMD; MCDR1) is a rare autosomal dominant congenital macular developmental disorder with variable expressivity. It is caused by noncoding regulatory variants or tandem duplications that disrupt cis-regulatory control of retinal developmental transcription factors, especially PRDM13 and, at the MCDR3 locus, IRX1. Affected individuals show a broad macular phenotype ranging from drusen-like deposits to severe coloboma-like macular malformations, with variably reduced central vision.
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name: North Carolina Macular Dystrophy
creation_date: "2026-05-11T00:00:00Z"
updated_date: "2026-05-11T00:00:00Z"
category: Mendelian
description: >
North Carolina macular dystrophy (NCMD; MCDR1) is a rare autosomal dominant
congenital macular developmental disorder with variable expressivity. It is
caused by noncoding regulatory variants or tandem duplications that disrupt
cis-regulatory control of retinal developmental transcription factors,
especially PRDM13 and, at the MCDR3 locus, IRX1. Affected individuals show a
broad macular phenotype ranging from drusen-like deposits to severe
coloboma-like macular malformations, with variably reduced central vision.
disease_term:
preferred_term: North Carolina macular dystrophy
term:
id: MONDO:0007630
label: North Carolina macular dystrophy
synonyms:
- NCMD
- MCDR1
- CAPE dystrophy
- CAPED
- central areolar pigment epithelial dystrophy
parents:
- Macular Dystrophy
- Retinal Dystrophy
- Ophthalmological Disease
inheritance:
- name: Autosomal dominant
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
description: >
NCMD segregates as an autosomal dominant macular dystrophy. Published
pedigrees show marked variable expressivity, from grade 1 drusen-like
lesions to severe bilateral coloboma-like macular malformations.
evidence:
- reference: PMID:37008391
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Four subjects from 3 generations were found to have macular abnormalities."
explanation: >
Affected individuals across three generations in this Mexican family
support dominant vertical transmission.
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations."
explanation: >
This family study explicitly classifies NCMD as autosomal dominant and
emphasizes phenotypic variability.
pathophysiology:
- name: Cis-Regulatory PRDM13 Dysregulation
description: >
NCMD-associated noncoding variants cluster in regulatory elements near
PRDM13, and tandem duplications can include PRDM13 or nearby DNase I
hypersensitive regulatory sites. These variants alter retinal enhancer
activity and dysregulate PRDM13 during central retinal development.
gene:
preferred_term: PRDM13
modifier: DYSREGULATED
term:
id: hgnc:13998
label: PRDM13
cell_types:
- preferred_term: amacrine cell
term:
id: CL:0000561
label: amacrine cell
- preferred_term: retinal ganglion cell
term:
id: CL:0000740
label: retinal ganglion cell
biological_processes:
- preferred_term: regulation of transcription by RNA polymerase II
modifier: DYSREGULATED
term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
- preferred_term: amacrine cell differentiation
modifier: DYSREGULATED
term:
id: GO:0035881
label: amacrine cell differentiation
evidence:
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1."
explanation: >
The discovery study connects NCMD-causing variants to PRDM13-mediated
macular development and raises IRX1 dysregulation for the chromosome 5
linked form.
- reference: PMID:36243009
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "Overall, this study provides insight into the cis-regulatory mechanisms of NCMD and supports that this condition is a retinal enhanceropathy."
explanation: >
This integrated multi-omics and functional assay study frames NCMD as a
retinal enhanceropathy.
downstream:
- target: Congenital Macular Developmental Disruption
- name: IRX1 Regulatory Dysregulation
description: >
A distinct MCDR3 locus involves a large duplication including IRX1. The
causal mechanism is less resolved than the PRDM13 hotspot mechanism, but
current evidence supports developmental dysregulation of IRX1 as a second
regulatory route to NCMD-like macular maldevelopment.
gene:
preferred_term: IRX1
modifier: DYSREGULATED
term:
id: hgnc:14358
label: IRX1
biological_processes:
- preferred_term: regulation of transcription by RNA polymerase II
modifier: DYSREGULATED
term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
evidence:
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5)."
explanation: >
The original sequencing study identifies a chromosome 5 MCDR3 duplication
including IRX1 in individuals with NCMD.
downstream:
- target: Congenital Macular Developmental Disruption
- name: Congenital Macular Developmental Disruption
description: >
Dysregulated retinal developmental transcriptional control arrests or
disrupts human macular development. The resulting lesions are congenital or
present in early infancy and usually do not progress between clinical grades.
cell_types:
- preferred_term: retinal pigment epithelial cell
term:
id: CL:0002586
label: retinal pigment epithelial cell
- preferred_term: photoreceptor cell
term:
id: CL:0000210
label: photoreceptor cell
- preferred_term: amacrine cell
term:
id: CL:0000561
label: amacrine cell
biological_processes:
- preferred_term: photoreceptor cell development
modifier: DYSREGULATED
term:
id: GO:0042461
label: photoreceptor cell development
- preferred_term: amacrine cell differentiation
modifier: DYSREGULATED
term:
id: GO:0035881
label: amacrine cell differentiation
evidence:
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We identified 5 rare mutations, each capable of arresting human macular development."
explanation: >
The human genetic discovery paper directly supports arrested macular
development as the central pathological process.
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD."
explanation: >
The Chinese family study links the PRDM13-region duplication to the
characteristic macular lesion spectrum.
downstream:
- target: Macular dystrophy
- target: Reduced central visual acuity
- target: Choroidal neovascularization
- name: PRDM13-Dependent Amacrine Cell Specification
description: >
Model-organism data support a developmental role for Prdm13 in amacrine
cell subtype specification. This does not by itself model the human macula,
but it supports the plausibility that altered PRDM13 regulation disrupts
retinal developmental circuitry.
cell_types:
- preferred_term: glycinergic amacrine cell
term:
id: CL:4030028
label: glycinergic amacrine cell
biological_processes:
- preferred_term: amacrine cell differentiation
modifier: DYSREGULATED
term:
id: GO:0035881
label: amacrine cell differentiation
evidence:
- reference: DOI:10.1186/s13064-017-0093-2
supports: PARTIAL
evidence_source: MODEL_ORGANISM
snippet: "Conversely, knockdown of prdm13 specifically inhibits glycinergic amacrine cell genesis."
explanation: >
Xenopus data support PRDM13 involvement in amacrine cell development, but
this is model-organism evidence and does not reproduce a human macula.
phenotypes:
- name: Macular dystrophy
description: >
NCMD is a congenital or early-onset macular dystrophy with variable lesion
severity. Mild disease can resemble macular drusen, whereas severe disease
can present with large coloboma-like macular malformations.
phenotype_term:
preferred_term: Macular dystrophy
term:
id: HP:0007754
label: Macular dystrophy
onset:
onset_category: INFANTILE
evidence:
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD."
explanation: >
The study describes the broad macular lesion spectrum in genetically
confirmed NCMD.
- name: Macular drusen
description: >
Grade 1 or mild NCMD can present with drusen-like macular lesions.
phenotype_term:
preferred_term: Macular drusen
term:
id: HP:0030499
label: Macular drusen
evidence:
- reference: PMID:37008391
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The 80-year-old mother of the proband had drusen-like lesions consistent with grade 1 NCMD."
explanation: >
This family report directly documents drusen-like lesions as grade 1
NCMD.
- name: Macular atrophy
description: >
More severe NCMD lesions can show large central thinning or excavation with
loss of macular tissue, clinically resembling atrophic or coloboma-like
macular malformation.
phenotype_term:
preferred_term: Macular atrophy
term:
id: HP:0007401
label: Macular atrophy
evidence:
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "OCT revealed varying degrees of macular structure disorganization."
explanation: >
OCT evidence supports structural macular disruption in NCMD.
- name: Reduced central visual acuity
description: >
Central visual acuity is variably affected. Some affected individuals have
relatively preserved acuity, whereas severe lesions or complications can
cause substantial central vision loss.
phenotype_term:
preferred_term: Reduced visual acuity
term:
id: HP:0007663
label: Reduced visual acuity
evidence:
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The BCVA ranged from 20/50 to 20/20."
explanation: >
Best-corrected visual acuity measurements in this family demonstrate
variable visual acuity.
- reference: PMID:37008391
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The proband presented with lifelong bilateral vision impairment with bilaterally symmetric vitelliform Best disease-like appearing macular lesions."
explanation: >
Lifelong bilateral vision impairment supports reduced visual acuity or
central visual function as a clinical phenotype.
- name: Central scotoma
description: >
Central scotoma can occur when macular lesions affect the fixation point.
phenotype_term:
preferred_term: Central scotoma
term:
id: HP:0000603
label: Central scotoma
evidence:
- reference: PMID:37008391
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "The proband presented with lifelong bilateral vision impairment with bilaterally symmetric vitelliform Best disease-like appearing macular lesions."
explanation: >
The abstract supports central macular visual impairment but does not
specifically report formal visual-field testing, so this is partial
support for central scotoma.
- name: Choroidal neovascularization
description: >
Choroidal neovascularization is a vision-threatening complication of NCMD
that can present with intraretinal and subretinal fluid and respond to
anti-VEGF treatment.
phenotype_term:
preferred_term: Choroidal neovascularization
term:
id: HP:0011506
label: Choroidal neovascularization
evidence:
- reference: DOI:10.1097/icb.0000000000000838
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Optical coherence tomography examination showed intraretinal and subretinal fluid consistent with CNV."
explanation: >
This case report directly documents CNV in an individual with NCMD.
genetic:
- name: PRDM13 regulatory variants and duplications
gene_term:
preferred_term: PRDM13
term:
id: hgnc:13998
label: PRDM13
association: Causative
notes: >
Pathogenic NCMD variants include noncoding SNVs in a DNase I hypersensitive
regulatory region upstream of PRDM13 and tandem duplications involving
PRDM13 or its regulatory landscape. These variants act through regulatory
dysregulation rather than a simple coding loss-of-function mechanism.
evidence:
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes."
explanation: >
The discovery paper identifies the original noncoding PRDM13-region
regulatory variant.
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A complete duplication of the PRDM13 gene was also discovered in a single family (V4)."
explanation: >
This supports PRDM13-region structural variation as a causal mechanism.
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A novel 134.6 kb (g.99932464-100067110dup) tandem duplication on chromosome 6 (NC_000006.11) encompassing the entire CCNC and PRDM13 genes and a DNase 1 hypersensitivity site in the MCDR1 locus was identified."
explanation: >
This family study expands the causal duplication spectrum at the PRDM13
MCDR1 locus.
- reference: PMID:37008391
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This suggests that this site, chr6:99593030, is a mutational hotspot."
explanation: >
The 2023 report supports a PRDM13 regulatory mutational hotspot.
- name: IRX1-region duplication
gene_term:
preferred_term: IRX1
term:
id: hgnc:14358
label: IRX1
association: Causative
notes: >
MCDR3-linked NCMD has been associated with a tandem duplication including
IRX1. The mechanism is interpreted as developmental regulatory
dysregulation, but PRDM13-region variants remain the better-established
recurrent NCMD mechanism.
evidence:
- reference: PMID:26507665
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5)."
explanation: >
This supports an IRX1-containing structural variant as the genetic lesion
at the MCDR3 locus.
diagnosis:
- name: Multimodal ophthalmic evaluation
description: >
Clinical diagnosis is based on characteristic macular lesions assessed with
fundus examination and retinal imaging, including OCT, fundus photography,
autofluorescence, ERG, and EOG when needed.
diagnosis_term:
preferred_term: eye examination
term:
id: MAXO:0001155
label: eye examination
evidence:
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Detailed ophthalmological examinations were performed, including best corrected visual acuity (BCVA), slit lamp, dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence, full-field electroretinography (ERG), and electrooculography (EOG)."
explanation: >
This describes the multimodal ophthalmic workup used in a genetically
confirmed NCMD family.
- name: Optical coherence tomography
description: >
OCT helps define macular structure, identify disorganization or thinning,
and detect intraretinal or subretinal fluid when CNV complicates NCMD.
diagnosis_term:
preferred_term: optical coherence tomography
term:
id: MAXO:0000969
label: optical coherence tomography
evidence:
- reference: PMID:34427740
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "OCT revealed varying degrees of macular structure disorganization."
explanation: >
OCT directly demonstrated variable macular structural abnormalities in
NCMD.
- reference: DOI:10.1097/icb.0000000000000838
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Optical coherence tomography examination showed intraretinal and subretinal fluid consistent with CNV."
explanation: >
OCT detected fluid consistent with CNV, a treatable complication.
- name: Molecular genetic testing
description: >
Whole-genome sequencing, copy-number analysis, breakpoint confirmation, or
targeted testing of the PRDM13/IRX1 regulatory loci can confirm the
molecular diagnosis.
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
evidence:
- reference: PMID:37008391
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Whole-genome sequencing (WGS) was performed followed by variant filtering and copy number variant analysis."
explanation: >
The 2023 family report used WGS and CNV analysis to identify the causal
noncoding mutation.
- reference: DOI:10.1097/icb.0000000000000838
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genetic testing of the PRDM13 gene can confirm a molecular diagnosis for North Carolina macular dystrophy."
explanation: >
This case report explicitly supports PRDM13 genetic testing for molecular
diagnosis.
treatments:
- name: Anti-VEGF therapy for CNV
description: >
NCMD itself has no established disease-modifying therapy, but choroidal
neovascularization can be treated with intravitreal anti-VEGF therapy.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: bevacizumab
term:
id: NCIT:C2039
label: Bevacizumab
target_phenotypes:
- preferred_term: Choroidal neovascularization
term:
id: HP:0011506
label: Choroidal neovascularization
evidence:
- reference: DOI:10.1097/icb.0000000000000838
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The visual acuity improved from 20/400 to 20/150 in the right eye and from 20/100 to 20/40 in the left eye after intravitreal bevacizumab treatment for CNV."
explanation: >
Case evidence supports anti-VEGF treatment for NCMD-associated CNV.
- name: Genetic counseling
description: >
Genetic counseling is appropriate for affected families because NCMD is an
autosomal dominant disorder with variable expressivity and molecular testing
can confirm the causal regulatory variant or duplication.
treatment_term:
preferred_term: genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
evidence:
- reference: PMID:34427740
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations."
explanation: >
The inheritance pattern and variable phenotype support genetic counseling,
although the cited abstract does not directly evaluate counseling outcomes.
datasets:
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North Carolina macular dystrophy (NCMD; also referenced as MCDR1) is a rare, autosomal dominant, congenital macular malformation/developmental maculopathy with marked variable expressivity but (reported) complete/fully penetrant inheritance in many families. It is typically described as nonprogressive (i.e., lesions are present at birth/early infancy and do not usually advance in “grade”), although vision-threatening complications such as choroidal neovascularization (CNV) can occur and can be treatable with anti-VEGF therapy. Mechanistically, NCMD is now widely characterized as a “retinal enhanceropathy,” in which noncoding single-nucleotide variants (SNVs) and tandem duplications perturb cis-regulatory elements controlling developmental retinal transcription factors—most prominently PRDM13 (MCDR1, chr6) and IRX1 (MCDR3, chr5)—disrupting developmental programs and macula-centric retinal organization. (small2023newnoncodingbase pages 1-2, sompele2022multiomicsapproachdissects pages 1-3)
NCMD is a congenital macular developmental disorder typically present at birth and usually described as stable/nonprogressive. A recent report states: “NCMD/MCDR1; OMIM #136550” and defines it as “autosomal dominant, fully penetrant, congenital, nonprogressive macular malformation with marked intrafamilial phenotypic variability.” (small2023newnoncodingbase pages 1-2)
A separate cohort paper states directly: “NCMD is present at birth and rarely progresses.” (green2021northcarolinamacular pages 1-6)
Not retrieved in the tool-accessible full-text set: MONDO ID, Orphanet ID, MeSH term, ICD-10/ICD-11 code. These identifiers likely exist in curated databases, but were not present in the retrieved primary/review texts and therefore cannot be stated with tool-derived evidence here. (wu2022anoveltandem pages 1-3, sompele2022multiomicsprofilingin pages 25-27)
Evidence in this report is derived from peer-reviewed primary studies (human family genetics; functional assays; case reports), a 2023 clinical electrophysiology review, and preprint computational analysis; it is not derived from EHR aggregation. (small2016northcarolinamacular pages 1-2, sompele2022multiomicsapproachdissects pages 13-14, chiang2023electrophysiologicalevaluationof pages 11-12)
Primary cause: inherited noncoding regulatory variation that dysregulates key retinal developmental transcription factors. - The 2022 AJHG multi-omics study summarizes the causal architecture: NCMD is caused by “non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications overlapping DNase I hypersensitive sites near PRDM13 or IRX1,” framing NCMD as a “retinal enhanceropathy.” (sompele2022multiomicsapproachdissects pages 1-3) - A 2023 family study reinforces that the phenotype is consistent with a regulatory “mutational hotspot” upstream of PRDM13. (small2023newnoncodingbase pages 1-2)
Inheritance pattern: autosomal dominant (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3)
No protective alleles or gene–environment interaction evidence was identified in the retrieved texts. (sompele2022multiomicsapproachdissects pages 1-3)
A 2023 clinical genetics report describes a three-grade spectrum and explicitly states approximate frequency distribution: “approximately one-third of affected individuals in each clinical grade.” (small2023newnoncodingbase pages 1-2) - Grade 1: few central drusen / central drusen-like deposits (small2023newnoncodingbase pages 1-2) - Grade 2: confluent drusen ± subretinal fibrosis (small2023newnoncodingbase pages 1-2) - Grade 3: choroidal coloboma-like excavation/large central atrophic excavation with absent RPE/choroidal lacunae and surrounding fibrosis (small2023newnoncodingbase pages 1-2)
Below, phenotype types are indicated and mapped to suggested HPO terms (ontology suggestions are not claims of curated mapping).
1) Macular developmental lesions / drusen-like deposits (clinical sign) - Evidence: range from “central yellowish-white drusen-like deposits” to confluent drusen-like lesions (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3) - Suggested HPO: Macular dystrophy (HP:0000556); Drusen (HP:0001132); Macular coloboma / coloboma-like macular lesion (candidate: Coloboma (HP:0000589) with localization qualifier)
2) Macular excavation / chorioretinal atrophy-like appearance (clinical sign) - Grade 3 described as coloboma-like excavation with absent RPE/choroidal lacunae (small2023newnoncodingbase pages 1-2) - Suggested HPO: Chorioretinal atrophy (HP:0001130); Abnormality of the macula (HP:0001103)
3) Reduced central vision / variable visual acuity (symptom/function) - Quantitative evidence: visual acuity range reported as 0.0–1.6 LogMAR in one cohort (green2021northcarolinamacular pages 1-6) - Suggested HPO: Decreased visual acuity (HP:0007663); Central scotoma (HP:0000603) (central scotomata documented in one child) (audere2016geneticlinkagestudies pages 4-6)
4) Peripheral retinal spots/drusen-like changes (clinical sign) - “Peripheral retinal spots were seen in all study subjects on widefield imaging.” (green2021northcarolinamacular pages 1-6) - Suggested HPO: Peripheral retinal degeneration (HP:0001133) (approximate); Retinal deposits (candidate)
5) Choroidal neovascularization (CNV/CNVM) (complication) - CNV can occur in childhood: “a 6-year-old patient developed choroidal neovascularization and required treatment with intravitreal bevacizumab injections.” (green2021northcarolinamacular pages 1-6) - Suggested HPO: Choroidal neovascularization (HP:0000559); Subretinal fibrosis (HP:0007897)
Direct QoL instruments (EQ-5D/SF-36) were not reported in the retrieved texts. Functional impact is inferred via central vision impairment and scotoma when present. (audere2016geneticlinkagestudies pages 4-6, green2021northcarolinamacular pages 1-6)
Noncoding SNVs (regulatory/DHS) upstream of PRDM13 - Example coordinates cited in cohorts/analyses include chr6:100,040,906G>T, chr6:100,040,974A>C, chr6:100,040,987G>C, chr6:100,041,040C>T, chr6:100,046,783A>C (hg19/GRCh37 as specified in the original sources) (green2021northcarolinamacular pages 28-31) - 2023 report notes a new base-pair mutation at the identical locus as the original, supporting a hotspot. (small2023newnoncodingbase pages 1-2)
Tandem duplications (structural variants) - 2016 Ophthalmology describes duplications including a 123 kb tandem duplication containing PRDM13 and a 900 kb tandem duplication including IRX1 (small2016northcarolinamacular pages 4-5) - 2022 Chinese family reports a 134.6 kb tandem duplication with explicit coordinate interval: g.99932464-100067110dup (chr6) encompassing CCNC, PRDM13, and a DHS (publication date 2022-08) (wu2022anoveltandem pages 1-3)
Functional directionality (cis-regulatory output) — multi-omics 2022 AJHG Luciferase assays (in vitro) systematically showed allele-dependent effects: - Hotspot-1 variants increased reporter expression 1.6–3.2-fold (p<0.001), while hotspot-2 variants decreased expression to ~0.6–0.7-fold (p<0.001). (sompele2022multiomicsapproachdissects pages 13-14) - Tandem duplication constructs produced ~0.5-fold decreased luciferase activity relative to single-copy constructs. (sompele2022multiomicsapproachdissects pages 13-14)
No modifier genes or disease-specific epigenetic signatures were identified in the retrieved evidence. Structural variants are tandem duplications rather than aneuploidy/translocations. (sompele2022multiomicsapproachdissects pages 13-14, wu2022anoveltandem pages 1-3)
No environmental, lifestyle, or infectious contributors were identified in the retrieved literature; NCMD is presented as a congenital genetic developmental malformation. (green2021northcarolinamacular pages 1-6, small2023newnoncodingbase pages 1-2)
The strongest mechanistic synthesis is from the 2022 AJHG multi-omics study: - Upstream event: noncoding SNVs in mutational hotspots and duplications spanning candidate cis-regulatory elements (cCREs) near PRDM13 and IRX1 alter enhancer activity and/or gene regulatory landscape. (sompele2022multiomicsapproachdissects pages 1-3, sompele2022multiomicsapproachdissects pages 13-14) - Regulatory wiring: UMI-4C (adult human retina) plus integrated retina epigenomics nominated 18 cCREs, and functional assays (luciferase; Xenopus enhancer assays) showed disease-associated variants change enhancer output. (sompele2022multiomicsapproachdissects pages 1-3) - Developmental timing/cell types: single-nucleus RNA-seq indicates PRDM13 is predominantly expressed in amacrine cells (and some retinal progenitors/horizontal/ganglion cells) and IRX1 peaks in retinal ganglion cells, with developmental peaks around embryonic timepoints (e.g., e70). This supports the hypothesis that altered PRDM13/IRX1 expression impairs “amacrine–ganglion cell” interactions during retinogenesis. (sompele2022multiomicsapproachdissects pages 13-14, sompele2022multiomicsapproachdissects pages 1-3)
Suggested ontology mappings (mechanism; non-exhaustive): - GO Biological Process: retina development; neurogenesis; amacrine cell differentiation; synapse organization - Cell Ontology (CL) candidates: amacrine cell, retinal ganglion cell, retinal progenitor cell (supported by expression localization and developmental claims) (sompele2022multiomicsapproachdissects pages 13-14)
A Xenopus study provides developmental mechanism support for PRDM13 function: - prdm13 is expressed in retinal progenitors and ~40% of amacrine cells, predominantly glycinergic; knockdown “prevents glycinergic cell genesis,” while overexpression biases toward amacrine fate with glycinergic preference. (publication date 2017-09) (bessodes2017prdm13formsa pages 1-2, bessodes2017prdm13formsa pages 10-13) These developmental roles align with the AJHG study’s cell-type timing (amacrine emergence and synapsing with ganglion cells) and support a plausible causal chain from regulatory dysregulation to disrupted macular/central retinal wiring. (sompele2022multiomicsapproachdissects pages 1-3, sompele2022multiomicsapproachdissects pages 13-14)
Suggested UBERON terms (candidates): - retina, macula lutea, fovea centralis, retinal pigment epithelium (RPE)
Formal prevalence/incidence rates were not identified in the retrieved texts.
However, several quantitative or semi-quantitative epidemiology statements are available: - “NCMD is rare but reported worldwide in >50 families.” (small2023newnoncodingbase pages 1-2) - “More than 2000 patients have been diagnosed worldwide.” (wu2022anoveltandem pages 1-3) - Historical founder kindred: original pedigree described as >500 individuals across seven generations (green2021northcarolinamacular pages 1-6), and a “very large kindred (~2000 individuals)” is referenced in linkage-era literature (audere2016geneticlinkagestudies pages 1-2).
Multimodal ophthalmic evaluation is emphasized, including: - Fundus examination/photography for drusen-like deposits, confluent changes, or excavation (wu2022anoveltandem pages 1-3) - OCT: in mild grade 1 lesions can show RPE-level deposits with preserved ellipsoid zone; severe lesions can show “central intrachoroidal fluid-containing space with preserved retinal layers,” and CNV/subretinal fibrosis may be visible in advanced disease. (chiang2023electrophysiologicalevaluationof pages 11-12) - Widefield imaging: peripheral spots “seen in all study subjects” can support recognition. (green2021northcarolinamacular pages 1-6)
The 2023 electrophysiology review provides test interpretation patterns: - Full-field ERG often normal in NCMD (suggesting absence of generalized photoreceptor dysfunction). (chiang2023electrophysiologicalevaluationof pages 11-12) - mfERG abnormal (delayed implicit times and reduced amplitudes localized to central lesion), helping detect macular dysfunction when ffERG is normal. (chiang2023electrophysiologicalevaluationof pages 11-12, chiang2023electrophysiologicalevaluationof pages 12-14) - EOG abnormal with reduced LP:DT (Arden) ratios reported 1.4–1.6, consistent with RPE dysfunction. (chiang2023electrophysiologicalevaluationof pages 11-12)
Evidence-supported approaches include: - Whole genome sequencing (WGS) and targeted confirmation (Sanger) for noncoding SNVs and breakpoint characterization; CNV analysis for tandem duplications. (small2023newnoncodingbase pages 1-2) - Long-read or genome sequencing can validate tandem duplications (reported in the Chinese family study). (wu2022anoveltandem pages 1-3)
Mortality/survival outcomes are not applicable (ocular-limited disorder) and not reported in retrieved evidence.
No disease-modifying pharmacotherapy or gene therapy was identified for NCMD in the retrieved evidence. Current care is primarily monitoring and treating complications.
Suggested MAXO terms (candidates): - intravitreal injection; anti-VEGF therapy; optical coherence tomography (diagnostic procedure); low vision rehabilitation (not explicitly described in retrieved texts, but relevant as supportive care)
A tool-based clinicaltrials.gov search retrieved trials metadata but no specific, NCMD-targeted interventional clinical trials were identified in the retrieved evidence set.
No primary prevention is described for NCMD (genetic congenital disorder). Secondary prevention is essentially cascade screening and early ophthalmic monitoring in affected families to detect CNV early and treat promptly. (small2023newnoncodingbase pages 1-2, green2021northcarolinamacular pages 13-16)
No naturally occurring NCMD-equivalent disease in companion animals was identified in the retrieved evidence.
Non-human models do not possess a human-like macula, so they primarily model retinal developmental circuitry and cis-regulatory logic, not macula anatomy per se. The macula-predominant phenotype therefore requires careful cross-species interpretation and may be best modeled with human retinal organoids and human multi-omics integration (explicitly proposed as a future direction). (sompele2022multiomicsprofilingin pages 25-27)
Genetic schematics of the original variant set (V1–V5) and their locus contexts are shown in the cropped figures retrieved from Small et al. (Ophthalmology, 2016-01). These illustrate the PRDM13-region regulatory SNVs/duplication (V1–V4) and the IRX1-region duplication (V5). (small2016northcarolinamacular media 3981bb1f, small2016northcarolinamacular media deebfcdf)
The following evidence-grounded table consolidates identifiers, loci/genes, variant examples, inheritance, and hallmark phenotypes/complications.
| Item type | Detail | Evidence/Notes |
|---|---|---|
| Disease identifier | North Carolina macular dystrophy (NCMD); OMIM/MIM #136550 | Reported explicitly as “NCMD [MIM: 136550]” / “NCMD/MCDR1; OMIM #136550” in evidence; rare congenital macular disorder (small2023newnoncodingbase pages 1-2, sompele2022multiomicsprofilingin pages 25-27) |
| Locus name | MCDR1 | Chromosome 6 locus upstream of PRDM13; commonly used alternative locus-based identifier for NCMD (small2023newnoncodingbase pages 1-2, small2016northcarolinamacular pages 1-2, wu2022anoveltandem pages 1-3, sompele2022multiomicsprofilingin pages 25-27) |
| Locus name | MCDR3 | Chromosome 5 locus involving/downstream of IRX1; additional NCMD locus (small2023newnoncodingbase pages 1-2, small2016northcarolinamacular pages 1-2, wu2022anoveltandem pages 1-3, bakall2021choroidalneovascularizationin pages 5-5, sompele2022multiomicsprofilingin pages 25-27) |
| Gene | PRDM13 | Main disease-implicated transcription factor at MCDR1; NCMD is described as caused by dysregulation of PRDM13 rather than coding loss-of-function alone (small2016northcarolinamacular pages 4-5, small2016northcarolinamacular pages 1-2, sompele2022multiomicsapproachdissects pages 1-3) |
| Gene | IRX1 | Implicated at MCDR3 through downstream duplications or duplication including IRX1; proposed dysregulation mechanism (small2016northcarolinamacular pages 1-2, bakall2021choroidalneovascularizationin pages 5-5, sompele2022multiomicsapproachdissects pages 1-3) |
| Gene context | CCNC | Present in the MCDR1 region context; a novel chr6 tandem duplication encompassed CCNC, PRDM13, and a DNase I hypersensitive site. CCNC OMIM 123838 given in evidence, but causal role is less established than PRDM13 dysregulation (wu2022anoveltandem pages 1-3) |
| Inheritance | Autosomal dominant | Consistently described as autosomal dominant in multiple studies/reviews (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3, green2021northcarolinamacular pages 1-6) |
| Penetrance | Fully penetrant | Explicitly stated in 2023 evidence: “autosomal dominant, fully penetrant, congenital” with marked intrafamilial variability (small2023newnoncodingbase pages 1-2) |
| Expressivity | Marked intra- and interfamilial variability | Visual acuity and lesion severity vary widely despite shared familial variants; variable expressivity repeatedly emphasized (small2023newnoncodingbase pages 1-2, green2021northcarolinamacular pages 1-6) |
| Variant type | Noncoding SNV upstream of PRDM13: chr6:100,040,906G>T (hg19) | Original NCMD-associated regulatory variant in DNase hypersensitivity site upstream of PRDM13 (bakall2021choroidalneovascularizationin pages 5-5, green2021northcarolinamacular pages 28-31) |
| Variant type | Noncoding SNV upstream of PRDM13: chr6:100,040,974A>C (hg19) | Reported disease-associated variant within PRDM13 regulatory enhancer region (green2021northcarolinamacular pages 28-31) |
| Variant type | Noncoding SNV upstream of PRDM13: chr6:100,040,987G>C (hg19/GRCh37) | Detected in all affected members of one cohort/families; predicted to lie in enhancer interacting with PRDM13 (green2021northcarolinamacular pages 1-6, green2021northcarolinamacular pages 28-31) |
| Variant type | Noncoding SNV upstream of PRDM13: chr6:100,041,040C>T (hg19) | Additional NCMD-associated variant in same regulatory region (green2021northcarolinamacular pages 28-31) |
| Variant type | Noncoding SNV near PRDM13 enhancer: chr6:100,046,783A>C (hg19) | Candidate enhancer variant predicted functional in macular/retinal tissue (green2021northcarolinamacular pages 28-31) |
| Variant type | 123-kb tandem duplication containing PRDM13 | Structural variant reported at MCDR1 in a family; supports dosage/regulatory mechanism (small2016northcarolinamacular pages 4-5, bakall2021choroidalneovascularizationin pages 5-5) |
| Variant type | 134.6-kb tandem duplication at chr6 g.99932464-100067110dup | Novel duplication in a Chinese family; encompasses CCNC, PRDM13, and a DNase I hypersensitive site in MCDR1 (wu2022anoveltandem pages 1-3) |
| Variant type | 900-kb tandem duplication including entire IRX1 gene (V5) | Reported at MCDR3 locus on chromosome 5; segregated with disease (small2016northcarolinamacular pages 4-5, small2016northcarolinamacular pages 1-2) |
| Variant mechanism | Retinal enhanceropathy / cis-regulatory dysregulation | Pathogenic SNVs cluster in PRDM13 mutational hotspots/cCREs; duplications may duplicate one or more CREs or disturb gene regulatory landscape affecting PRDM13 or IRX1 expression (sompele2022multiomicsapproachdissects pages 13-14, sompele2022multiomicsapproachdissects pages 1-3, sompele2022multiomicsprofilingin pages 25-27) |
| Clinical phenotype | Congenital, usually nonprogressive macular developmental disorder | Present at birth; typically little progression, though phenotype severity is variable (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3, green2021northcarolinamacular pages 1-6) |
| Clinical phenotype | Grade 1 lesion | Central yellowish-white/drusen-like deposits; early OCT may show RPE-level deposits with intact ellipsoid zone (wu2022anoveltandem pages 1-3, chiang2023electrophysiologicalevaluationof pages 11-12) |
| Clinical phenotype | Grade 2 lesion | Larger confluent drusen-like/confluent macular changes, sometimes with subretinal fibrosis (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3) |
| Clinical phenotype | Grade 3 lesion | Large central atrophic excavation / choroidal coloboma-like lesion with absent RPE/choroidal lacunae in severe disease descriptions (small2023newnoncodingbase pages 1-2, wu2022anoveltandem pages 1-3) |
| Clinical phenotype | Peripheral retinal spots | Widefield imaging can reveal peripheral radial yellow-white/drusen-like spots; useful clinical clue (green2021northcarolinamacular pages 1-6, green2021northcarolinamacular pages 28-31) |
| Visual function | Visual acuity highly variable | Reported range 0.0 to 1.6 LogMAR in one series; acuity can remain relatively preserved despite large lesions (green2021northcarolinamacular pages 1-6, wu2022anoveltandem pages 1-3) |
| Complication | Choroidal neovascularization (CNV/CNVM) | Can occur in childhood/early life; one 6-year-old required treatment; advanced disease may show CNV and subretinal fibrosis (green2021northcarolinamacular pages 1-6, bakall2021choroidalneovascularizationin pages 5-5, chiang2023electrophysiologicalevaluationof pages 11-12) |
| Management note | Anti-VEGF response for CNV | Intravitreal bevacizumab reported beneficial / vision-improving in NCMD-associated CNV (green2021northcarolinamacular pages 1-6, bakall2021choroidalneovascularizationin pages 5-5) |
Table: This table summarizes evidence-supported identifiers, loci, causal genes, variant classes, inheritance, and hallmark clinical features of North Carolina macular dystrophy. It is designed as a compact reference for disease knowledge base curation using only facts present in the retrieved evidence snippets.
1) Expanded mutational spectrum and hotspot concept (2023): identification of an additional noncoding base change at the same regulatory locus as the original MCDR1 family supports a mutational hotspot model and reiterates “autosomal dominant, fully penetrant, congenital, nonprogressive” disease framing. (Small et al., 2023-01; URL https://doi.org/10.1177/24741264221129432) (small2023newnoncodingbase pages 1-2)
2) Expert clarification of developmental terminology (2023): commentary emphasizes NCMD is better described as congenital macular hypoplasia/dysplasia, cautioning against misleading descriptors such as “atrophy” and reinforcing locus nomenclature (MCDR1/MCDR3). (Small, 2023-09; URL https://doi.org/10.1186/s12886-023-03100-2) (small2023commentson“the pages 1-2)
3) Clinical electrophysiology integration (2023): contemporary review consolidates the typical pattern (normal ffERG, abnormal mfERG, abnormal EOG with LP:DT ~1.4–1.6) and highlights how electrophysiology localizes dysfunction and supports differential diagnosis among macular dystrophies. (Chiang & Yu, 2023-02; URL https://doi.org/10.3390/jcm12041430) (chiang2023electrophysiologicalevaluationof pages 11-12)
References
(small2023newnoncodingbase pages 1-2): Kent W. Small, Stijn Van de Sompele, Jessica Avetisjan, Nitin Udar, Steven Agemy, Elfride De Baere, and Fadi S. Shaya. New noncoding base pair mutation at the identical locus as the original ncmd/mcdr1 in a mexican family, suggesting a mutational hotspot. Journal of VitreoRetinal Diseases, 7:33-42, Jan 2023. URL: https://doi.org/10.1177/24741264221129432, doi:10.1177/24741264221129432. This article has 3 citations.
(sompele2022multiomicsapproachdissects pages 1-3): Stijn Van de Sompele, Kent W. Small, Munevver Burcu Cicekdal, Víctor López Soriano, Eva D’haene, Fadi S. Shaya, Steven Agemy, Thijs Van der Snickt, Alfredo Dueñas Rey, Toon Rosseel, Mattias Van Heetvelde, Sarah Vergult, Irina Balikova, Arthur A. Bergen, Camiel J.F. Boon, Julie De Zaeytijd, Chris F. Inglehearn, Bohdan Kousal, Bart P. Leroy, Carlo Rivolta, Veronika Vaclavik, Jenneke van den Ende, Mary J. van Schooneveld, José Luis Gómez-Skarmeta, Juan J. Tena, Juan R. Martinez-Morales, Petra Liskova, Kris Vleminckx, and Elfride De Baere. Multi-omics approach dissects cis-regulatory mechanisms underlying north carolina macular dystrophy, a retinal enhanceropathy. The American Journal of Human Genetics, 109:2029-2048, Nov 2022. URL: https://doi.org/10.1016/j.ajhg.2022.09.013, doi:10.1016/j.ajhg.2022.09.013. This article has 27 citations.
(green2021northcarolinamacular pages 1-6): David J. Green, Eva Lenassi, Cerys S. Manning, David McGaughey, Vinod Sharma, Graeme C. Black, Jamie M. Ellingford, and Panagiotis I. Sergouniotis. North carolina macular dystrophy: phenotypic variability and computational analysis of disease-implicated non-coding variants. MedRxiv, Mar 2021. URL: https://doi.org/10.1101/2021.03.05.21252975, doi:10.1101/2021.03.05.21252975. This article has 3 citations.
(sompele2022multiomicsprofilingin pages 25-27): Stijn Van de Sompele, Kent W. Small, Munevver Burcu Cicekdal, Víctor López Soriano, Eva D’haene, Fadi S. Shaya, Steven Agemy, Thijs Van der Snickt, Alfredo Dueñas Rey, Toon Rosseel, Mattias Van Heetvelde, Sarah Vergult, Irina Balikova, Arthur A. Bergen, Camiel J. F. Boon, Julie De Zaeytijd, Chris F. Inglehearn, Bohdan Kousal, Bart P. Leroy, Carlo Rivolta, Veronika Vaclavik, Jenneke van den Ende, Mary J. van Schooneveld, José Luis Gómez-Skarmeta, Juan J. Tena, Juan R. Martinez-Morales, Petra Liskova, Kris Vleminckx, and Elfride De Baere. Multi-omics profiling, in vitro and in vivo enhancer assays dissect the cis-regulatory mechanisms underlying north carolina macular dystrophy, a retinal enhanceropathy. bioRxiv, Jul 2022. URL: https://doi.org/10.1101/2022.03.08.481329, doi:10.1101/2022.03.08.481329. This article has 2 citations.
(small2016northcarolinamacular pages 1-2): Kent W. Small, Adam P. DeLuca, S. Scott Whitmore, Thomas Rosenberg, Rosemary Silva-Garcia, Nitin Udar, Bernard Puech, Charles A. Garcia, Thomas A. Rice, Gerald A. Fishman, Elise Héon, James C. Folk, Luan M. Streb, Christine M. Haas, Luke A. Wiley, Todd E. Scheetz, John H. Fingert, Robert F. Mullins, Budd A. Tucker, and Edwin M. Stone. North carolina macular dystrophy is caused by dysregulation of the retinal transcription factor prdm13. Ophthalmology, 123 1:9-18, Jan 2016. URL: https://doi.org/10.1016/j.ophtha.2015.10.006, doi:10.1016/j.ophtha.2015.10.006. This article has 143 citations and is from a highest quality peer-reviewed journal.
(wu2022anoveltandem pages 1-3): Shijing Wu, Zhisheng Yuan, Zixi Sun, Tian Zhu, Xing Wei, Xuan Zou, and Ruifang Sui. A novel tandem duplication of prdm13 in a chinese family with north carolina macular dystrophy. Graefe's Archive for Clinical and Experimental Ophthalmology, 260:645-653, Aug 2022. URL: https://doi.org/10.1007/s00417-021-05376-w, doi:10.1007/s00417-021-05376-w. This article has 11 citations.
(bakall2021choroidalneovascularizationin pages 5-5): MD Benjamin Bakall, †. J. Shepard, MD Bryan III, MD Edwin M. Stone, and MD Kent W. Small. Choroidal neovascularization in north carolina macular dystrophy responsive to anti–vascular endothelial growth factor therapy. RETINAL Cases & Brief Reports, 15:509-513, Sep 2021. URL: https://doi.org/10.1097/icb.0000000000000838, doi:10.1097/icb.0000000000000838. This article has 19 citations and is from a peer-reviewed journal.
(small2023commentson“the pages 1-2): Kent W. Small. Comments on “the possible pathogenesis of macular caldera in patients with north carolina macular dystrophy”. BMC Ophthalmology, Sep 2023. URL: https://doi.org/10.1186/s12886-023-03100-2, doi:10.1186/s12886-023-03100-2. This article has 0 citations and is from a peer-reviewed journal.
(sompele2022multiomicsapproachdissects pages 13-14): Stijn Van de Sompele, Kent W. Small, Munevver Burcu Cicekdal, Víctor López Soriano, Eva D’haene, Fadi S. Shaya, Steven Agemy, Thijs Van der Snickt, Alfredo Dueñas Rey, Toon Rosseel, Mattias Van Heetvelde, Sarah Vergult, Irina Balikova, Arthur A. Bergen, Camiel J.F. Boon, Julie De Zaeytijd, Chris F. Inglehearn, Bohdan Kousal, Bart P. Leroy, Carlo Rivolta, Veronika Vaclavik, Jenneke van den Ende, Mary J. van Schooneveld, José Luis Gómez-Skarmeta, Juan J. Tena, Juan R. Martinez-Morales, Petra Liskova, Kris Vleminckx, and Elfride De Baere. Multi-omics approach dissects cis-regulatory mechanisms underlying north carolina macular dystrophy, a retinal enhanceropathy. The American Journal of Human Genetics, 109:2029-2048, Nov 2022. URL: https://doi.org/10.1016/j.ajhg.2022.09.013, doi:10.1016/j.ajhg.2022.09.013. This article has 27 citations.
(chiang2023electrophysiologicalevaluationof pages 11-12): Tsun-Kang Chiang and Minzhong Yu. Electrophysiological evaluation of macular dystrophies. Journal of Clinical Medicine, 12:1430, Feb 2023. URL: https://doi.org/10.3390/jcm12041430, doi:10.3390/jcm12041430. This article has 7 citations.
(audere2016geneticlinkagestudies pages 4-6): Mareta Audere, Katrina Rutka, Inna Inaskina, Raitis Peculis, Svetlana Sepetiene, Sandra Valeina, and Baiba Lāce. Genetic linkage studies of a north carolina macular dystrophy family. Medicina, 52 3:180-6, Jan 2016. URL: https://doi.org/10.1016/j.medici.2016.04.001, doi:10.1016/j.medici.2016.04.001. This article has 10 citations.
(small2016northcarolinamacular pages 4-5): Kent W. Small, Adam P. DeLuca, S. Scott Whitmore, Thomas Rosenberg, Rosemary Silva-Garcia, Nitin Udar, Bernard Puech, Charles A. Garcia, Thomas A. Rice, Gerald A. Fishman, Elise Héon, James C. Folk, Luan M. Streb, Christine M. Haas, Luke A. Wiley, Todd E. Scheetz, John H. Fingert, Robert F. Mullins, Budd A. Tucker, and Edwin M. Stone. North carolina macular dystrophy is caused by dysregulation of the retinal transcription factor prdm13. Ophthalmology, 123 1:9-18, Jan 2016. URL: https://doi.org/10.1016/j.ophtha.2015.10.006, doi:10.1016/j.ophtha.2015.10.006. This article has 143 citations and is from a highest quality peer-reviewed journal.
(green2021northcarolinamacular pages 28-31): David J. Green, Eva Lenassi, Cerys S. Manning, David McGaughey, Vinod Sharma, Graeme C. Black, Jamie M. Ellingford, and Panagiotis I. Sergouniotis. North carolina macular dystrophy: phenotypic variability and computational analysis of disease-implicated non-coding variants. MedRxiv, Mar 2021. URL: https://doi.org/10.1101/2021.03.05.21252975, doi:10.1101/2021.03.05.21252975. This article has 3 citations.
(bessodes2017prdm13formsa pages 1-2): Nathalie Bessodes, Karine Parain, Odile Bronchain, Eric J. Bellefroid, and Muriel Perron. Prdm13 forms a feedback loop with ptf1a and is required for glycinergic amacrine cell genesis in the xenopus retina. Neural Development, Sep 2017. URL: https://doi.org/10.1186/s13064-017-0093-2, doi:10.1186/s13064-017-0093-2. This article has 26 citations and is from a peer-reviewed journal.
(bessodes2017prdm13formsa pages 10-13): Nathalie Bessodes, Karine Parain, Odile Bronchain, Eric J. Bellefroid, and Muriel Perron. Prdm13 forms a feedback loop with ptf1a and is required for glycinergic amacrine cell genesis in the xenopus retina. Neural Development, Sep 2017. URL: https://doi.org/10.1186/s13064-017-0093-2, doi:10.1186/s13064-017-0093-2. This article has 26 citations and is from a peer-reviewed journal.
(bakall2021choroidalneovascularizationin pages 2-5): MD Benjamin Bakall, †. J. Shepard, MD Bryan III, MD Edwin M. Stone, and MD Kent W. Small. Choroidal neovascularization in north carolina macular dystrophy responsive to anti–vascular endothelial growth factor therapy. RETINAL Cases & Brief Reports, 15:509-513, Sep 2021. URL: https://doi.org/10.1097/icb.0000000000000838, doi:10.1097/icb.0000000000000838. This article has 19 citations and is from a peer-reviewed journal.
(audere2016geneticlinkagestudies pages 1-2): Mareta Audere, Katrina Rutka, Inna Inaskina, Raitis Peculis, Svetlana Sepetiene, Sandra Valeina, and Baiba Lāce. Genetic linkage studies of a north carolina macular dystrophy family. Medicina, 52 3:180-6, Jan 2016. URL: https://doi.org/10.1016/j.medici.2016.04.001, doi:10.1016/j.medici.2016.04.001. This article has 10 citations.
(chiang2023electrophysiologicalevaluationof pages 12-14): Tsun-Kang Chiang and Minzhong Yu. Electrophysiological evaluation of macular dystrophies. Journal of Clinical Medicine, 12:1430, Feb 2023. URL: https://doi.org/10.3390/jcm12041430, doi:10.3390/jcm12041430. This article has 7 citations.
(green2021northcarolinamacular pages 13-16): David J. Green, Eva Lenassi, Cerys S. Manning, David McGaughey, Vinod Sharma, Graeme C. Black, Jamie M. Ellingford, and Panagiotis I. Sergouniotis. North carolina macular dystrophy: phenotypic variability and computational analysis of disease-implicated non-coding variants. MedRxiv, Mar 2021. URL: https://doi.org/10.1101/2021.03.05.21252975, doi:10.1101/2021.03.05.21252975. This article has 3 citations.
(chiang2023electrophysiologicalevaluationof pages 7-9): Tsun-Kang Chiang and Minzhong Yu. Electrophysiological evaluation of macular dystrophies. Journal of Clinical Medicine, 12:1430, Feb 2023. URL: https://doi.org/10.3390/jcm12041430, doi:10.3390/jcm12041430. This article has 7 citations.
(nekolova2022moderndiagnosticand pages 2-6): Jana Nekolova, Alexandr Stepanov, Bohdan Kousal, Marketa Stredova, and Nada Jiraskova. Modern diagnostic and therapeutic approaches in familial maculopathy with reference to north carolina macular dystrophy. Biomedical Papers, 166:418-427, Dec 2022. URL: https://doi.org/10.5507/bp.2021.037, doi:10.5507/bp.2021.037. This article has 4 citations.
(small2016northcarolinamacular media 3981bb1f): Kent W. Small, Adam P. DeLuca, S. Scott Whitmore, Thomas Rosenberg, Rosemary Silva-Garcia, Nitin Udar, Bernard Puech, Charles A. Garcia, Thomas A. Rice, Gerald A. Fishman, Elise Héon, James C. Folk, Luan M. Streb, Christine M. Haas, Luke A. Wiley, Todd E. Scheetz, John H. Fingert, Robert F. Mullins, Budd A. Tucker, and Edwin M. Stone. North carolina macular dystrophy is caused by dysregulation of the retinal transcription factor prdm13. Ophthalmology, 123 1:9-18, Jan 2016. URL: https://doi.org/10.1016/j.ophtha.2015.10.006, doi:10.1016/j.ophtha.2015.10.006. This article has 143 citations and is from a highest quality peer-reviewed journal.
(small2016northcarolinamacular media deebfcdf): Kent W. Small, Adam P. DeLuca, S. Scott Whitmore, Thomas Rosenberg, Rosemary Silva-Garcia, Nitin Udar, Bernard Puech, Charles A. Garcia, Thomas A. Rice, Gerald A. Fishman, Elise Héon, James C. Folk, Luan M. Streb, Christine M. Haas, Luke A. Wiley, Todd E. Scheetz, John H. Fingert, Robert F. Mullins, Budd A. Tucker, and Edwin M. Stone. North carolina macular dystrophy is caused by dysregulation of the retinal transcription factor prdm13. Ophthalmology, 123 1:9-18, Jan 2016. URL: https://doi.org/10.1016/j.ophtha.2015.10.006, doi:10.1016/j.ophtha.2015.10.006. This article has 143 citations and is from a highest quality peer-reviewed journal.