RGD Reference Report - Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia. - Rat Genome Database

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Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia.

Authors: Boyden, LM  Craiglow, BG  Zhou, J  Hu, R  Loring, EC  Morel, KD  Lauren, CT  Lifton, RP  Bilguvar, K  Paller, AS  Choate, KA  Choate, KA 
Citation: Boyden LM, etal., J Invest Dermatol. 2015 Jun;135(6):1540-7. doi: 10.1038/jid.2014.485. Epub 2014 Nov 14.
RGD ID: 11568612
Pubmed: PMID:25398053   (View Abstract at PubMed)
PMCID: PMC4430428   (View Article at PubMed Central)
DOI: DOI:10.1038/jid.2014.485   (Journal Full-text)

Genetic investigation of inherited skin disorders has informed the understanding of skin self-renewal, differentiation, and barrier function. Erythrokeratodermia variabilis et progressiva (EKVP) is a rare, inherited skin disease that is characterized by transient figurate patches of erythema, localized or generalized scaling, and frequent palmoplantar keratoderma. By using exome sequencing, we show that de novo missense mutations in GJA1 (gap junction protein alpha 1) cause EKVP. The severe, progressive skin disease in EKVP subjects with GJA1 mutations is distinct from limited cutaneous findings rarely found in the systemic disorder oculodentodigital dysplasia, also caused by dominant GJA1 mutations. GJA1 encodes connexin 43 (Cx43), the most widely expressed gap junction protein. We show that the GJA1 mutations in EKVP subjects lead to disruption of Cx43 membrane localization and aggregation within the Golgi. These findings reveal a critical role for Cx43 in epidermal homeostasis, and they provide evidence of organ-specific pathobiology resulting from different mutations within GJA1.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
GJA1Humanerythrokeratodermia variabilis  IAGP DNA:mutations:cds:p.E227D and p.A44V(human)RGD 
Gja1Raterythrokeratodermia variabilis  ISOGJA1 (Homo sapiens)DNA:mutations:cds:p.E227D and p.A44V(human)RGD 
Gja1Mouseerythrokeratodermia variabilis  ISOGJA1 (Homo sapiens)DNA:mutations:cds:p.E227D and p.A44V(human)RGD 


Genes (Rattus norvegicus)
Gja1  (gap junction protein, alpha 1)

Genes (Mus musculus)
Gja1  (gap junction protein, alpha 1)

Genes (Homo sapiens)
GJA1  (gap junction protein alpha 1)