GJB2 – Bart-Pumphrey Syndrome

Bart-Pumphrey syndrome (MONDO:0007866) is an autosomal dominant ectodermal dysplasia characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads and leukonychia. A novel heterozygous missense variant c.162C>G (p.Asn54Lys) in GJB2 segregated with the phenotype in a single family (4 affected individuals) and was absent in 110 ethnically matched controls (PMID:15482471). Immunostaining of lesional palmar and knuckle skin showed markedly reduced Cx26 with preserved adnexal expression, accompanied by compensatory overexpression of Cx30, consistent with a dominant-negative or loss-of-function mechanism (PMID:15482471). These data establish GJB2 as a causative gene for Bart-Pumphrey syndrome.

Key Take-home: GJB2 mutation screening should be included in the diagnostic evaluation of autosomal dominant syndromic hearing loss with palmoplantar keratoderma.

References

• The Journal of investigative dermatology • 2004 • Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey syndrome is caused by a novel missense mutation in GJB2. PMID:15482471

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