Home / Deep Research / Junctional Epidermolysis Bullosa

Junctional Epidermolysis Bullosa

1. Disease Information

2026-05-09
Falcon MONDO:0017612 Model: Edison Scientific Literature 52 citations

1. Disease Information

1.1 What is the disease?

JEB is an EB subtype defined by cleavage within the lamina lucida at the epithelial–subepithelial junction, producing mucocutaneous blistering and erosions. It is a rare autosomal recessive genodermatosis with broad phenotypic variability and systemic involvement (e.g., gastrointestinal, renal, respiratory). (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)

1.2 Key identifiers (available in retrieved evidence)

  • MONDO: MONDO_0017612 (junctional epidermolysis bullosa) (OpenTargets Search: Junctional epidermolysis bullosa)
  • Related MONDO terms listed in the same ontology context:
  • JEB, non-Herlitz type: MONDO_0009180 (OpenTargets Search: Junctional epidermolysis bullosa)
  • JEB, Herlitz type: MONDO_0009182 (OpenTargets Search: Junctional epidermolysis bullosa)
  • JEB with pyloric atresia: MONDO_0009183 (OpenTargets Search: Junctional epidermolysis bullosa)

Not retrieved in this tool run (evidence unavailable here): OMIM numbers, Orphanet IDs, ICD-10/ICD-11 codes, MeSH IDs. (No citeable context in this run.)

1.3 Synonyms / alternative names (from retrieved evidence)

1.4 Evidence source type

This report is based on aggregated disease-level resources and peer-reviewed literature (reviews, cohort studies, registry epidemiology, guidelines), supplemented by clinical trial registry entries (ClinicalTrials.gov). (wen2024genotype–phenotypecorrelationin pages 13-17, chen2025identificationofdeep pages 1-2, NCT03526159 chunk 1)

2. Etiology

2.1 Disease causal factors

Primary cause: inherited pathogenic variants in genes encoding proteins required for dermal–epidermal adhesion at the basement membrane zone, producing defective adhesion and tissue cleavage in the lamina lucida. (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)

2.2 Risk factors

Environmental risk factors as causes of JEB are not applicable (monogenic disease); environmental exposures mainly influence complications (wound infection, trauma). (keith2020leadingedgeemerging pages 1-6)

2.3 Protective factors

No established genetic or environmental protective factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

Not specifically addressed in the retrieved evidence; clinically, mechanical trauma and infection interact with genetic skin fragility to drive lesion burden. (keith2020leadingedgeemerging pages 1-6)

3. Phenotypes

3.1 Core phenotype spectrum (with HPO suggestions)

Commonly reported features include: - Skin and mucosal blistering/erosions after minor trauma; chronic wounds (HPO: Skin blistering; Erosions) (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17) - Nail dystrophy / anonychia (HPO: Nail dystrophy, Anonychia) (wen2024genotype–phenotypecorrelationin pages 13-17, murashkin2024congenitalepidermolysisbullosa pages 1-2) - Enamel defects (HPO: Enamel hypoplasia) (wen2024genotype–phenotypecorrelationin pages 13-17) - Scarring / alopecia (HPO: Scarring, Alopecia) (wen2024genotype–phenotypecorrelationin pages 13-17) - Airway/laryngeal involvement (laryngotracheal stenosis, airway obstruction) (HPO: Laryngeal stenosis, Tracheal stenosis, Respiratory distress) (lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4) - Ocular involvement (HPO: Eye irritation/erosion—non-quantified here) (wen2024genotype–phenotypecorrelationin pages 13-17) - Anemia, failure to thrive, sepsis risk (HPO: Anemia, Failure to thrive, Sepsis) (wen2024genotype–phenotypecorrelationin pages 13-17, murashkin2024congenitalepidermolysisbullosa pages 1-2)

3.2 Phenotype characteristics (onset, severity, progression)

  • Onset: typically congenital/neonatal or early infancy (widespread blistering and erosions). (wen2024genotype–phenotypecorrelationin pages 13-17, murashkin2024congenitalepidermolysisbullosa pages 1-2)
  • Severe JEB (Herlitz/generalized severe): often fatal in early childhood, with mortality linked to sepsis, dehydration, airway obstruction, metabolic disturbances. (wen2024genotype–phenotypecorrelationin pages 13-17, bischof2024emerginggenetherapeutics pages 1-2)
  • Intermediate JEB: survival into adulthood, heterogeneous course with chronic wounds and extracutaneous involvement. (wen2024genotype–phenotypecorrelationin pages 13-17)

3.3 Quality of life impact

QoL instruments/statistics specific to JEB were not retrieved in the available evidence; however, airway-involved EB patients experience high morbidity and require repeated airway procedures. (lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4)

4. Genetic / Molecular Information

4.1 Causal genes (human)

From a 2024 genotype–phenotype study and ontology evidence, JEB is caused by pathogenic variants in: - LAMA3, LAMB3, LAMC2 (laminin-332 chains) - COL17A1 (type XVII collagen) - ITGA6, ITGB4 (integrin α6β4) - ITGA3 (integrin α3) (wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22, OpenTargets Search: Junctional epidermolysis bullosa)

4.2 Variant classes and functional consequences

Common variant types include nonsense, frameshift, splice-site, deletions, and missense variants. (wen2024genotype–phenotypecorrelationin pages 17-22)

Genotype–phenotype correlation (severity): - Biallelic premature termination codon (PTC) / loss-of-function variants in laminin-332 genes often lead to severe JEB due to nonsense-mediated decay and absent laminin-332 staining. (wen2024genotype–phenotypecorrelationin pages 17-22) - Non–loss-of-function alleles (missense/in-frame changes/exon skipping) can preserve partial protein; ~5–10% residual laminin-332 may meaningfully ameliorate severity. (wen2024genotype–phenotypecorrelationin pages 17-22)

4.3 Modifier genes

Mouse-model genetic evidence supports strong modifier effects: - Col17a1 identified as a major genetic modifier of Lamc2 hypomorphic JEB severity in mice; 1–3 amino-acid differences in the NC4 domain of collagen XVII altered dermal–epidermal adhesion and disease severity. (Sproule et al., 2014; https://doi.org/10.1371/journal.pgen.1004068) (sproule2014molecularidentificationof pages 1-2) - Additional modifier loci/QTL reported in Lamc2jeb mice include intervals containing Dst-e/Bpag1-e and candidate metabolic/nuclear receptor pathways (Ppargc1a, Pparg, Igf1). (Sproule et al., 2023; https://doi.org/10.1371/journal.pone.0288263) (sproule2023sevennaturallyvariant pages 1-2)

4.4 Deep intronic variants and diagnostic “missing heritability”

A 2025 study highlights that exome sequencing can miss causative alleles: - Among 69 recessive JEB cases, 13.0% remained genetically undiagnosed after initial exome sequencing; among COL17A1-associated cases, unresolved proportion reached 31.6%. (Chen et al., 2025; https://doi.org/10.1038/s41525-025-00466-8) (chen2025identificationofdeep pages 1-2) - Deep intronic variants identified: COL17A1 c.4156+117G>A, c.2039-104G>A, c.1267+237dupC and LAMB3 c.-38+2T>C in six cases; splicing assays showed exon skipping/pseudoexon insertion in HaCaT cells but not HEK293, emphasizing cell-context dependence of transcript assays. (chen2025identificationofdeep pages 1-2)

5. Environmental Information

JEB is monogenic; no specific toxins/lifestyle/infectious agents were identified as causes. Environmental factors (mechanical trauma, wound colonization/infection) act as downstream exacerbators of disease burden and complications. (keith2020leadingedgeemerging pages 1-6)

6. Mechanism / Pathophysiology

6.1 Causal chain (molecular → clinical)

  1. Biallelic pathogenic variants in laminin-332 / COL17A1 / integrin genes reduce/abolish functional adhesion complexes at the basement membrane zone. (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 17-22)
  2. Defective hemidesmosomes / dermal–epidermal adhesion at the lamina lucida causes mechanical fragility. (keith2020leadingedgeemerging pages 1-6, NCT03526159 chunk 1)
  3. Minimal trauma leads to blistering and erosions, evolving into chronic wounds. (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17)
  4. Chronic wounds promote inflammation, infection risk, fluid/protein loss, and systemic complications including failure to thrive, anemia, and sepsis. (wen2024genotype–phenotypecorrelationin pages 13-17, murashkin2024congenitalepidermolysisbullosa pages 1-2)

6.2 Cell types and processes (ontology suggestions)

  • Key cell types (CL): basal keratinocytes; airway epithelial basal stem cells (supported by Human Lung Cell Atlas expression context and primary basal-cell experiments). (lau2024lentiviralexpressionof pages 2-4)
  • Biological processes (GO suggestions): cell–substrate adhesion; hemidesmosome assembly; basement membrane organization; wound healing; epithelial cell differentiation. Mechanistic relevance is supported by the central role of laminin-332 and by gene-restoration phenotypes in airway basal cells. (lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 4-5)

6.3 Molecular profiling / advanced technologies

Direct multi-omics profiling for JEB was not retrieved in available evidence; however, Lau et al. performed RNA-seq after LAMA3A transduction in EB airway basal cells and observed 373 differentially expressed transcripts (149 up, 224 down), consistent with broad epithelial phenotype shifts. (lau2024lentiviralexpressionof pages 4-5)

7. Anatomical Structures Affected

7.1 Organ/system involvement

7.2 Tissue/cell level

  • Basement membrane zone of stratified epithelia; basal epithelial attachment structures are central. (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 17-22)

8. Temporal Development

8.1 Onset

Typically at birth or in the first months of life. (murashkin2024congenitalepidermolysisbullosa pages 1-2, wen2024genotype–phenotypecorrelationin pages 13-17)

8.2 Progression/course

9. Inheritance and Population

9.1 Inheritance

JEB is primarily autosomal recessive. (wen2024genotype–phenotypecorrelationin pages 13-17, chandrasekaran2025cutaneoussquamouscell pages 1-2)

9.2 Epidemiology (statistics)

From Wen et al. (2024, J Invest Dermatol; https://doi.org/10.1016/j.jid.2023.11.021): - Incidence ~2.68 per million live births - Prevalence ~0.49 per million (wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)

Russian pediatric registry paper (Murashkin et al., 2024; https://doi.org/10.15690/vsp.v23i5.2808; accepted 16 Oct 2024): - 491 children with congenital EB in registry (all EB types) - 31 (6%) were junctional - Registry recorded 22 deaths, with JEB comprising 59.1% (13/22) and mean age at death 0.40 ± 0.22 years - Survival probability for JEB reportedly drops to almost 0% in the first 100 days (murashkin2024congenitalepidermolysisbullosa pages 2-3, murashkin2024congenitalepidermolysisbullosa pages 1-2)

Airway EB cohort (Lau et al., 2024; https://doi.org/10.1016/j.ymthe.2024.02.032): - 16 EB patients with airway disease; 8 had died at time of writing (lau2024lentiviralexpressionof pages 2-4)

10. Diagnostics

10.1 Recommended diagnostic modalities (laboratory and genetic)

Wen et al. (2024) describes a combined approach: - Genetic testing (Sanger, targeted NGS panels, WES/WGS) - Immunofluorescence mapping (IFM/antigen mapping) to localize cleavage plane and infer missing proteins - Transmission electron microscopy (TEM) for ultrastructural defects in selected cases (wen2024genotype–phenotypecorrelationin pages 13-17)

International laboratory guideline (Has et al., 2019; BJD; https://doi.org/10.1111/bjd.18128): - Genetic testing is “always recommended” and should include the index case and, if possible, parents for reliable counseling. - IFM is recommended for rapid diagnosis/prognosis and to prioritize genetics; TEM is reserved for limited inconclusive cases. - States: “DNA-based prenatal diagnosis is technically feasible for all EB subtypes” and should be considered upon family request/national regulations. (has2019clinicalpracticeguidelines pages 1-2, has2019clinicalpracticeguidelines pages 2-3)

10.2 Diagnostic yield improvements (WGS + splicing assays)

Genome sequencing can identify deep intronic alleles missed by exome; splicing assays require a relevant cell model (HaCaT vs HEK293) (chen2025identificationofdeep pages 1-2).

10.3 Differential diagnosis

Not comprehensively retrievable from the provided evidence in this run.

11. Outcome / Prognosis

11.1 Mortality and survival

11.2 Prognostic factors

Severity correlates with degree of residual protein (e.g., laminin-332) and mutation type (biallelic PTC/LoF vs residual expression). (wen2024genotype–phenotypecorrelationin pages 17-22)

12. Treatment

12.1 Standard-of-care (current real-world implementation)

Supportive multidisciplinary care remains foundational, including wound care, infection control, and systemic support (nutrition, pain management), as emphasized in both JEB-focused and EB-wide reviews. (keith2020leadingedgeemerging pages 1-6, danescu2024treatmentofepidermolysis pages 1-4)

12.2 Recently approved/marketed therapies (context)

A 2024 review notes that “the first drugs for the treatment of EB wounds in dystrophic and junctional EB have recently achieved US FDA and EMA approval” but does not specify product names in the excerpt. It also notes B-VEC licensing approval on May 19, 2023 for dystrophic EB as a milestone of in vivo gene therapy reaching clinical application. (Danescu et al., published online Aug 2, 2024; https://doi.org/10.1007/s13555-024-01227-8) (danescu2024treatmentofepidermolysis pages 1-4, danescu2024treatmentofepidermolysis pages 4-5)

12.3 Advanced therapeutics (gene/cell/RNA)

Ex vivo gene therapy for LAMB3-related JEB (skin): - Danescu et al. describes de Luca group’s “groundbreaking” life-saving transplantation of transgenic keratinocytes (80% TBSA) in intermediate JEB with LAMB3 mutations and notes that 5-year follow-up showed genetically repaired stem cells continued to regenerate near-normal epidermis. (danescu2024treatmentofepidermolysis pages 4-5) - A formal phase II/III protocol (Hologene 5; EudraCT 2018-000261-36; https://doi.org/10.3389/fgene.2021.705019) describes autologous keratinocytes corrected with γ-retroviral LAMB3 cDNA on fibrin support with 12-month efficacy endpoints and 15-year follow-up. (rosa2021hologene5a pages 1-2)

Nonsense suppression (gentamicin readthrough): - ClinicalTrials.gov pilot study: NCT03526159 (first posted 2018-05-16; last update posted 2020-04-07) evaluates topical (0.5% ointment BID ×14 days) and IV (7.5 mg/kg daily ×14 days) gentamicin in JEB patients with LAMB3 nonsense mutations; primary endpoints include laminin-332 immunofluorescence and EM hemidesmosomes; safety monitoring includes ototoxicity/nephrotoxicity and anti-laminin-332 antibodies. URL: https://clinicaltrials.gov/study/NCT03526159 (NCT03526159 chunk 1) - Optimization study: NCT04140786 (first posted 2019-10-28; last update posted 2022-11-03) tests IV gentamicin 10 mg/kg regimens and includes EB Disease Activity and Scarring Index (EBDASI) outcomes. URL: https://clinicaltrials.gov/study/NCT04140786 (NCT04140786 chunk 1)

Airway-directed combined cell/gene therapy proof-of-concept (2024): - Lau et al. (Molecular Therapy; accepted 27 Feb 2024; https://doi.org/10.1016/j.ymthe.2024.02.032) report airway disease in EB and show in vitro rescue of EB patient-derived airway basal cells by lentiviral LAMA3A expression. LAMA3 variants were found in 10/15 genotyped airway EB patients; basal cells showed adhesion defects. After transduction, LAMA3 mRNA increased 45.5-fold and 79.6-fold in two independent cultures; ALI cultures showed TEER within normal range (>250 Ω) and ciliary beat frequency within expected non-EB range (7–16 Hz); adhesion restored to near control. (lau2024lentiviralexpressionof pages 4-5, lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4)

12.4 MAXO suggestions (treatment action ontology; illustrative)

13. Prevention

13.1 Primary prevention

For Mendelian JEB, primary prevention focuses on reproductive options: - Has et al. (2019 guideline) states accurate EB diagnosis enables informed genetic counseling and prenatal/PGT options and that “DNA-based prenatal diagnosis is technically feasible for all EB subtypes”; prenatal diagnosis requires a known familial mutation. (has2019clinicalpracticeguidelines pages 1-2, has2019clinicalpracticeguidelines pages 2-3)

13.2 Secondary/tertiary prevention

14. Other Species / Natural Disease

Naturally occurring JEB has been reported in multiple domestic species and can inform genotype–phenotype correlations. - Cats (COL17A1): Two unrelated cats with homozygous COL17A1 splice(-region) variants showed marked severity differences; transcript analysis demonstrated residual wildtype splicing in the milder case, supporting a molecular basis for severity variation. (Genes, 2023; https://doi.org/10.3390/genes14101835) (natsuga2010animalmodelsof pages 1-2) - Dogs (LAMA3): A litter with severe mucocutaneous ulcers and upper airway obstruction had a novel LAMA3 missense variant with AR inheritance; EM confirmed lamina-lucida splitting. (Vet Dermatol, 2021; https://doi.org/10.1111/vde.12972) (not extracted as evidence snippet in gather_evidence, but paper is in state; no citeable context id provided beyond tool results)

Note: dog/horse/cat models are also referenced in EB animal-model reviews. (natsuga2010animalmodelsof pages 1-2)

15. Model Organisms

Recent developments (prioritizing 2023–2025 evidence retrieved here)

  1. Genotype–phenotype “signposts to severity” (2024): detailed correlation between LoF/PTC alleles and severe disease; residual laminin-332 (~5–10%) associated with milder/intermediate disease. (Wen et al., 2024; https://doi.org/10.1016/j.jid.2023.11.021) (wen2024genotype–phenotypecorrelationin pages 17-22)
  2. Airway gene therapy concepts (2024): first detailed pediatric airway cohort + in vitro LAMA3A lentiviral functional correction in airway basal cells, expanding the therapeutic target tissue beyond skin. (Lau et al., 2024; https://doi.org/10.1016/j.ymthe.2024.02.032) (lau2024lentiviralexpressionof pages 4-5, lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4)
  3. Genome sequencing resolves ES-negative JEB (2025): deep intronic COL17A1/LAMB3 variants and cell-type–specific splicing assay considerations. (Chen et al., 2025; https://doi.org/10.1038/s41525-025-00466-8) (chen2025identificationofdeep pages 1-2)

Evidence gaps in this tool run (explicit)

  • OMIM, Orphanet, ICD-10/ICD-11, and MeSH identifiers were not available in retrieved citeable evidence.
  • Detailed differential diagnosis tables and validated QoL statistics/instruments specific to JEB were not retrieved.
  • Human protective factors and gene–environment interaction datasets were not retrieved.

Structured summary table

Table (click to expand)
Topic Key details
Disease / identifiers Junctional epidermolysis bullosa (JEB); MONDO: MONDO_0017612. Open Targets also lists related subtype MONDO terms including JEB, non-Herlitz type (MONDO_0009180), JEB Herlitz type (MONDO_0009182), and JEB with pyloric atresia (MONDO_0009183). OMIM identifiers are not directly provided in the extracted evidence here. Disease is defined as an EB subtype with tissue cleavage in the lamina lucida / epithelial-subepithelial junction, usually inherited as autosomal recessive (https://platform.opentargets.org/disease/MONDO_0017612; 2026 access context) (OpenTargets Search: Junctional epidermolysis bullosa, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)
Main causal genes Core JEB genes repeatedly identified across recent evidence: LAMA3, LAMB3, LAMC2 (laminin-332 chains), COL17A1 (type XVII collagen), ITGA6, ITGB4 (integrin α6β4), and ITGA3. Open Targets disease-target evidence supports these as the principal disease-associated genes for JEB (https://platform.opentargets.org/disease/MONDO_0017612; context accessed 2026) (OpenTargets Search: Junctional epidermolysis bullosa, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)
Inheritance / molecular basis JEB is described as a rare autosomal recessive genodermatosis caused by loss or dysfunction of proteins required for dermal-epidermal adhesion. Laminin-332 deficiency, type XVII collagen deficiency, or integrin α6β4 dysfunction are major molecular categories (Wen et al., J Invest Dermatol, published Jun 2024, https://doi.org/10.1016/j.jid.2023.11.021; Keith et al., Mar 2020, https://doi.org/10.1080/14712598.2020.1740678) (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)
Subtypes / severity correlation Recent literature distinguishes severe/generalized severe (formerly Herlitz) versus intermediate/generalized intermediate (formerly non-Herlitz) JEB. Biallelic premature termination codon / loss-of-function variants in laminin-332 genes usually correlate with severe JEB, often with absent laminin-332 staining and early lethality; missense, splice-altering, in-frame, or exon-skipping alleles with residual protein expression (~5–10%) more often correlate with intermediate/milder disease. Severe JEB is often fatal in infancy/early childhood; intermediate JEB can survive into adulthood but remains multisystemic (Wen et al., Jun 2024, https://doi.org/10.1016/j.jid.2023.11.021; Bischof et al., Feb 2024, https://doi.org/10.3390/ijms25042243) (wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22, bischof2024emerginggenetherapeutics pages 1-2)
Clinical phenotype highlights Typical manifestations include widespread skin and mucosal blistering/erosions, chronic wounds, nail dystrophy/anonychia, enamel defects, scarring, alopecia, airway/laryngeal involvement, ocular involvement, anemia, and in severe forms failure to thrive, sepsis, and airway obstruction. Airway disease is especially linked to LAMA3-associated JEB severe / LOC-like disease (Wen et al., Jun 2024, https://doi.org/10.1016/j.jid.2023.11.021; Lau et al., May 2024, https://doi.org/10.1016/j.ymthe.2024.02.032) (wen2024genotype–phenotypecorrelationin pages 13-17, lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4)
Diagnostic modalities Key modalities include clinical phenotyping, immunofluorescence mapping (IFM / antigen mapping) to localize the cleavage plane and assess BMZ protein expression, transmission electron microscopy (TEM) for ultrastructural defects/hemidesmosomes, and molecular testing using Sanger sequencing, targeted panels, WES, and WGS/GS. Recent evidence shows a role for RNA/splicing assays when exome sequencing is inconclusive (Wen et al., Jun 2024, https://doi.org/10.1016/j.jid.2023.11.021; Chen et al., Feb 2025, https://doi.org/10.1038/s41525-025-00466-8) (wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22, chen2025identificationofdeep pages 1-2)
Diagnostic yield / deep intronic findings In a 2025 JEB genomics study of 69 recessive JEB cases, 13.0% remained genetically undiagnosed after initial exome sequencing; among COL17A1 cases, unresolved rate reached 31.6%. Genome sequencing plus splicing assays identified deep intronic variants COL17A1 c.4156+117G>A, c.2039-104G>A, c.1267+237dupC and LAMB3 c.-38+2T>C; these caused exon skipping or pseudoexon insertion in HaCaT keratinocyte cells but not HEK293 cells, supporting GS + cell-appropriate transcript testing for ES-negative JEB (Chen et al., published Feb 2025, https://doi.org/10.1038/s41525-025-00466-8) (chen2025identificationofdeep pages 1-2)
Epidemiology A 2024 genotype-phenotype study cites JEB incidence ~2.68 per million live births and prevalence ~0.49 per million. A 2020 review states JEB affects about 3 in 1 million children. Broader EB epidemiology reported in some recent reviews is higher because it covers all EB subtypes rather than JEB specifically (Wen et al., Jun 2024, https://doi.org/10.1016/j.jid.2023.11.021; Keith et al., Mar 2020, https://doi.org/10.1080/14712598.2020.1740678) (keith2020leadingedgeemerging pages 1-6, wen2024genotype–phenotypecorrelationin pages 13-17, wen2024genotype–phenotypecorrelationin pages 17-22)
Russian registry data (all congenital EB, with JEB-specific mortality note) Russian pediatric registry, publication accepted 16 Oct 2024 / journal issue 2024, DOI https://doi.org/10.15690/vsp.v23i5.2808: 491 children with congenital EB; pediatric prevalence 15.48 per 1,000,000; subtype distribution 261 dystrophic (53%), 191 simplex (39%), 31 junctional (6%), 8 Kindler (2%). Mean birth rate 2019–2023: 2.13 per 100,000 births. Registry recorded 22 deaths; JEB accounted for 59.1% of fatal outcomes (13/22) with mean age at death 0.40 ± 0.22 years; survival curve showed probability of survival falling to almost 0% in the first 100 days for JEB (Murashkin et al., 2024, https://doi.org/10.15690/vsp.v23i5.2808) (murashkin2024congenitalepidermolysisbullosa pages 2-3, murashkin2024congenitalepidermolysisbullosa pages 1-2)
Standard/current management Current standard of care remains supportive and multidisciplinary: blister lancing, atraumatic wound care, infection control, pain management, nutritional and systemic support, and treatment of complications. Reviews emphasize that despite therapeutic advances, most care remains palliative/symptom-directed (Keith et al., Mar 2020, https://doi.org/10.1080/14712598.2020.1740678; Danescu et al., published online Aug 2, 2024, https://doi.org/10.1007/s13555-024-01227-8) (keith2020leadingedgeemerging pages 1-6, danescu2024treatmentofepidermolysis pages 1-4)
Recently approved / wound-directed therapies relevant to EB A 2024 therapeutic review states that “the first drugs for the treatment of EB wounds in dystrophic and junctional EB have recently achieved US FDA and EMA approval”; it also notes that B-VEC became the first gene therapy clinically available for DEB on May 19, 2023, illustrating regulatory momentum in EB even though B-VEC is not JEB-specific (Danescu et al., Aug 2, 2024, https://doi.org/10.1007/s13555-024-01227-8) (danescu2024treatmentofepidermolysis pages 1-4, danescu2024treatmentofepidermolysis pages 4-5)
Gentamicin nonsense readthrough trials NCT03526159 (“Gentamicin for Junctional Epidermolysis Bullosa”; first posted 2018-05-16; recruiting per available registry snapshot) tests topical 0.5% gentamicin twice daily for 14 days or IV gentamicin 7.5 mg/kg daily for 14 days in JEB with LAMB3 nonsense mutations, with endpoints including laminin-332 IF signal, EM hemidesmosomes, wound closure, and safety. NCT04140786 (“Optimizing IV Gentamicin in JEB”; first posted 2019-10-28) studies 10 mg/kg IV regimens (daily x24 days or biweekly x3 months) in JEB with LAMA3/LAMB3 nonsense mutations, with endpoints including laminin-332 expression, EBDASI, ototoxicity, nephrotoxicity, and anti-laminin-332 antibodies (https://clinicaltrials.gov/study/NCT03526159; https://clinicaltrials.gov/study/NCT04140786) (NCT03526159 chunk 1, NCT03526159 chunk 2, NCT04140786 chunk 1, NCT04140786 chunk 2)
Ex vivo LAMB3 gene-corrected epidermal grafts Ex vivo autologous LAMB3-corrected keratinocyte / epidermal stem-cell grafting is the most mature JEB-specific gene-therapy paradigm. Hologene 5 (EudraCT 2018-000261-36; protocol paper 2021, https://doi.org/10.3389/fgene.2021.705019) is a phase II/III multicenter study using γ-retroviral full-length LAMB3 cDNA in autologous clonogenic keratinocytes on fibrin support for grafting. A 2024 review highlights prior life-saving transplantation over ~80% TBSA and durable 5-year maintenance of genetically repaired epidermis (Danescu et al., 2024; De Rosa et al., 2021) (rosa2021hologene5a pages 1-2, danescu2024treatmentofepidermolysis pages 4-5)
Airway-targeted gene/cell proof-of-concept In Lau et al. (Molecular Therapy, published May 2024, https://doi.org/10.1016/j.ymthe.2024.02.032), a cohort of 16 EB patients with airway disease was described; 10/15 genotyped patients had at least one LAMA3 pathogenic variant, median age at referral 9 months, and 8/16 had died by time of report. Patient airway basal cells showed adhesion defects; lentiviral LAMA3A overexpression increased LAMA3 mRNA by 45.5-fold and 79.6-fold in two cultures, enabled ALI differentiation with normal-range TEER (>250 Ω) and normal ciliary beat frequency (7–16 Hz), and restored adhesion to near non-EB control levels—supporting a future combined airway cell/gene therapy approach (lau2024lentiviralexpressionof pages 4-5, lau2024lentiviralexpressionof pages 1-2, lau2024lentiviralexpressionof pages 2-4)
Other/adjunct experimental wound therapies RGN-137 topical gel (thymosin β4-related wound-healing approach) was studied in JEB/DEB in NCT03578029 (CELEB), a randomized placebo-controlled phase II trial first posted 2018-07-05; status later terminated (business decision) with only 4 enrolled, illustrating the difficulty of wound-therapy trials in rare EB (https://clinicaltrials.gov/study/NCT03578029) (NCT03578029 chunk 1, NCT03578029 chunk 2)

Table: This table condenses the most clinically relevant facts about Junctional Epidermolysis Bullosa, including genes, inheritance, severity correlations, diagnostics, epidemiology, and current or emerging therapies. It is designed as a quick reference for building a disease knowledge base entry with directly citeable evidence contexts.

References

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  6. (lau2024lentiviralexpressionof pages 1-2): Chun Hang Lau, Maral J. Rouhani, Elizabeth F. Maughan, Jessica C. Orr, Krishna K. Kolluri, David R. Pearce, Elizabeth K. Haughey, Liam Sutton, Sam Flatau, Pablo Lopez Balboa, Maria Laura Bageta, Christopher O’Callaghan, Claire M. Smith, Sam M. Janes, Richard Hewitt, Gabriela Petrof, Anna E. Martinez, John A. McGrath, Colin R. Butler, and Robert E. Hynds. Lentiviral expression of wild-type lama3a restores cell adhesion in airway basal cells from children with epidermolysis bullosa. Molecular Therapy, 32:1497-1509, May 2024. URL: https://doi.org/10.1016/j.ymthe.2024.02.032, doi:10.1016/j.ymthe.2024.02.032. This article has 8 citations and is from a highest quality peer-reviewed journal.

  7. (bischof2024emerginggenetherapeutics pages 1-2): Johannes Bischof, Markus Hierl, and Ulrich Koller. Emerging gene therapeutics for epidermolysis bullosa under development. International Journal of Molecular Sciences, 25:2243, Feb 2024. URL: https://doi.org/10.3390/ijms25042243, doi:10.3390/ijms25042243. This article has 37 citations.

  8. (NCT03526159 chunk 1): David Woodley. Gentamicin for Junctional Epidermolysis Bullosa. University of Southern California. 2018. ClinicalTrials.gov Identifier: NCT03526159

  9. (murashkin2024congenitalepidermolysisbullosa pages 2-3): Nikolay N. Murashkin, Roman V. Epishev, Olga S. Orlova, Alena А. Kuratova, and Victoriya S. Polenova. Congenital epidermolysis bullosa epidemiology among children of russian federation. Current Pediatrics, 23:316-328, Oct 2024. URL: https://doi.org/10.15690/vsp.v23i5.2808, doi:10.15690/vsp.v23i5.2808. This article has 2 citations.

  10. (murashkin2024congenitalepidermolysisbullosa pages 1-2): Nikolay N. Murashkin, Roman V. Epishev, Olga S. Orlova, Alena А. Kuratova, and Victoriya S. Polenova. Congenital epidermolysis bullosa epidemiology among children of russian federation. Current Pediatrics, 23:316-328, Oct 2024. URL: https://doi.org/10.15690/vsp.v23i5.2808, doi:10.15690/vsp.v23i5.2808. This article has 2 citations.

  11. (lau2024lentiviralexpressionof pages 2-4): Chun Hang Lau, Maral J. Rouhani, Elizabeth F. Maughan, Jessica C. Orr, Krishna K. Kolluri, David R. Pearce, Elizabeth K. Haughey, Liam Sutton, Sam Flatau, Pablo Lopez Balboa, Maria Laura Bageta, Christopher O’Callaghan, Claire M. Smith, Sam M. Janes, Richard Hewitt, Gabriela Petrof, Anna E. Martinez, John A. McGrath, Colin R. Butler, and Robert E. Hynds. Lentiviral expression of wild-type lama3a restores cell adhesion in airway basal cells from children with epidermolysis bullosa. Molecular Therapy, 32:1497-1509, May 2024. URL: https://doi.org/10.1016/j.ymthe.2024.02.032, doi:10.1016/j.ymthe.2024.02.032. This article has 8 citations and is from a highest quality peer-reviewed journal.

  12. (sproule2014molecularidentificationof pages 1-2): Thomas J. Sproule, Jason A. Bubier, Fiorella C. Grandi, Victor Z. Sun, Vivek M. Philip, Caroline G. McPhee, Elisabeth B. Adkins, John P. Sundberg, and Derry C. Roopenian. Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice. PLoS Genetics, 10:e1004068, Feb 2014. URL: https://doi.org/10.1371/journal.pgen.1004068, doi:10.1371/journal.pgen.1004068. This article has 38 citations and is from a domain leading peer-reviewed journal.

  13. (sproule2023sevennaturallyvariant pages 1-2): Thomas J. Sproule, Vivek M. Philip, Nabig A. Chaudhry, Derry C. Roopenian, and John P. Sundberg. Seven naturally variant loci serve as genetic modifiers of lamc2jeb induced non-herlitz junctional epidermolysis bullosa in mice. PLOS ONE, 18:e0288263, Jul 2023. URL: https://doi.org/10.1371/journal.pone.0288263, doi:10.1371/journal.pone.0288263. This article has 7 citations and is from a peer-reviewed journal.

  14. (lau2024lentiviralexpressionof pages 4-5): Chun Hang Lau, Maral J. Rouhani, Elizabeth F. Maughan, Jessica C. Orr, Krishna K. Kolluri, David R. Pearce, Elizabeth K. Haughey, Liam Sutton, Sam Flatau, Pablo Lopez Balboa, Maria Laura Bageta, Christopher O’Callaghan, Claire M. Smith, Sam M. Janes, Richard Hewitt, Gabriela Petrof, Anna E. Martinez, John A. McGrath, Colin R. Butler, and Robert E. Hynds. Lentiviral expression of wild-type lama3a restores cell adhesion in airway basal cells from children with epidermolysis bullosa. Molecular Therapy, 32:1497-1509, May 2024. URL: https://doi.org/10.1016/j.ymthe.2024.02.032, doi:10.1016/j.ymthe.2024.02.032. This article has 8 citations and is from a highest quality peer-reviewed journal.

  15. (chandrasekaran2025cutaneoussquamouscell pages 1-2): Abarajithan Chandrasekaran and Justin C. Moser. Cutaneous squamous cell carcinoma in epidermolysis bullosa: a review of pathogenesis, diagnosis and management. Cancers, 17:3211, Oct 2025. URL: https://doi.org/10.3390/cancers17193211, doi:10.3390/cancers17193211. This article has 0 citations.

  16. (has2019clinicalpracticeguidelines pages 1-2): C. Has, L. Liu, M.C. Bolling, A.V. Charlesworth, M. El Hachem, M.J. Escámez, I. Fuentes, S. Büchel, R. Hiremagalore, G. Pohla‐Gubo, P.C. Akker, K. Wertheim‐Tysarowska, and G. Zambruno. Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa. The British Journal of Dermatology, 182:574-592, Aug 2019. URL: https://doi.org/10.1111/bjd.18128, doi:10.1111/bjd.18128. This article has 186 citations.

  17. (has2019clinicalpracticeguidelines pages 2-3): C. Has, L. Liu, M.C. Bolling, A.V. Charlesworth, M. El Hachem, M.J. Escámez, I. Fuentes, S. Büchel, R. Hiremagalore, G. Pohla‐Gubo, P.C. Akker, K. Wertheim‐Tysarowska, and G. Zambruno. Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa. The British Journal of Dermatology, 182:574-592, Aug 2019. URL: https://doi.org/10.1111/bjd.18128, doi:10.1111/bjd.18128. This article has 186 citations.

  18. (danescu2024treatmentofepidermolysis pages 1-4): Sorina Danescu, Mircea Negrutiu, and Cristina Has. Treatment of epidermolysis bullosa and future directions: a review. Dermatology and Therapy, 14:2059-2075, Aug 2024. URL: https://doi.org/10.1007/s13555-024-01227-8, doi:10.1007/s13555-024-01227-8. This article has 14 citations.

  19. (danescu2024treatmentofepidermolysis pages 4-5): Sorina Danescu, Mircea Negrutiu, and Cristina Has. Treatment of epidermolysis bullosa and future directions: a review. Dermatology and Therapy, 14:2059-2075, Aug 2024. URL: https://doi.org/10.1007/s13555-024-01227-8, doi:10.1007/s13555-024-01227-8. This article has 14 citations.

  20. (rosa2021hologene5a pages 1-2): Laura De Rosa, Elena Enzo, Giulia Zardi, Christine Bodemer, Cristina Magnoni, Holm Schneider, and Michele De Luca. Hologene 5: a phase ii/iii clinical trial of combined cell and gene therapy of junctional epidermolysis bullosa. Frontiers in Genetics, Sep 2021. URL: https://doi.org/10.3389/fgene.2021.705019, doi:10.3389/fgene.2021.705019. This article has 35 citations and is from a peer-reviewed journal.

  21. (NCT04140786 chunk 1): David Woodley. Optimizing IV Gentamicin in JEB. University of Southern California. 2019. ClinicalTrials.gov Identifier: NCT04140786

  22. (natsuga2010animalmodelsof pages 1-2): Ken Natsuga, Satoru Shinkuma, Wataru Nishie, and Hiroshi Shimizu. Animal models of epidermolysis bullosa. Dermatologic clinics, 28 1:137-42, Jan 2010. URL: https://doi.org/10.1016/j.det.2009.10.016, doi:10.1016/j.det.2009.10.016. This article has 32 citations and is from a peer-reviewed journal.

  23. (NCT03526159 chunk 2): David Woodley. Gentamicin for Junctional Epidermolysis Bullosa. University of Southern California. 2018. ClinicalTrials.gov Identifier: NCT03526159

  24. (NCT04140786 chunk 2): David Woodley. Optimizing IV Gentamicin in JEB. University of Southern California. 2019. ClinicalTrials.gov Identifier: NCT04140786

  25. (NCT03578029 chunk 1): Evaluation of the Safety and Efficacy Study of RGN-137 Topical Gel for Junctional and Dystrophic Epidermolysis Bullosa. Lenus Therapeutics, LLC. 2019. ClinicalTrials.gov Identifier: NCT03578029

  26. (NCT03578029 chunk 2): Evaluation of the Safety and Efficacy Study of RGN-137 Topical Gel for Junctional and Dystrophic Epidermolysis Bullosa. Lenus Therapeutics, LLC. 2019. ClinicalTrials.gov Identifier: NCT03578029