Ichthyosis and erythrokeratoderma

Gene: JUP

Comment on phenotypes: Previous phenotypes:
WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES;PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR;palmoplantar keratoderma (PPK), keratoderma with woolly hair;Naxos disease, 601214;KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Created: 23 Mar 2021, 2:32 p.m. | Last Modified: 23 Mar 2021, 2:32 p.m.

Panel Version: 1.31

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Palmoplantar keratoderma; cardiomyopathy; woolly hair; skin fragility; alopecia

Publications

• 20130592
• 21668431

Comment on mode of inheritance: Mode of inheritance supported by OMIM and Expert review.

Created: 20 Mar 2017, 10:27 a.m.

Comment on list classification: Updated rating from Amber to Green: 1 Green review plus >3 cases supporting PPK phenotype as part of Naxos disease.

Created: 20 Mar 2017, 10:26 a.m.

Comment on list classification: Updated rating from Red to Amber ready for Expert review. >3 unrelated cases of JUP variants linked to PPK phenotype and Naxos disease (OMIM:601214).

Created: 10 Jan 2017, 4:25 p.m.

>3 JUP variants listed in OMIM for Naxos disease (OMIM:601214), with 4 cases directly listing PPK/palmoplantar keratoderma as a phenotype:
In 3 unrelated Argentinian boys with skin fragility, PPK, and woolly hair, Cabral et al. (2010, PMID: 20130592) identified homozygosity for a nonsense mutation in the JUP gene. In affected members of 9 families and 3 sporadic patients with Naxos disease (NXD; OMIM:601214), all from the neighboring Greek islands of Naxos and Minos, McKoy et al. (2000, PMID:10902626) identified a 2-bp deletion at the 3' end of the plakoglobin (JUP) gene; all of the patients had ARVC, PPK, and woolly hair. In a Kuwaiti sister and brother with skin fragility, palmoplantar keratoderma, and sparse woolly hair (NXD; OMIM:601214), Cabral et al. (2010, PMID:20130592) identified homozygosity for a c.468G-A transition in exon 3 of the JUP gene. In 2 men from a consanguineous Turkish family with arrhythmogenic right ventricular cardiomyopathy, mild palmoplantar keratoderma, and alopecia (NXD; OMIM:601214), Erken et al. (2011, PMID:21668431) identified homozygosity for a c.794G-A transition in exon 4 of the JUP gene, resulting in a R265H substitution.

Created: 9 Jan 2017, 3 p.m.

Naxos disease (OMIM:601214) is an autosomal recessive disorder caused by homozygous mutation in the plakoglobin gene (JUP). The disease combines palmoplantar keratoderma (PPK) and other ectodermal features with cardiac disorders.

Created: 9 Jan 2017, 2:49 p.m.