Peeling Skin Syndrome 3

A number sign (#) is used with this entry because of evidence that peeling skin syndrome-3 (PSS3) is caused by mutation in the carbohydrate sulfotransferase-8 (CHST8; 610190) gene on chromosome 19q13. One such family has been reported.

Description

Peeling skin syndrome-3 is characterized by asymptomatic lifelong and continuous shedding of the stratum corneum of the epidermis. Symptoms start during the second half of the first decade of life and consist of generalized white scaling occurring over the upper and lower extremities (Cabral et al. (2012)).

For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).

Clinical Features

Cabral et al. (2012) described a 4-generation consanguineous Pakistani family with peeling skin syndrome. The 7 affected family members exhibited features of noninflammatory, painless peeling skin evidenced by generalized white scaling, most prominent over the upper and lower limbs. Their hair was normal. Affected individuals did not have a history of erythema, pruritis, or atopy; however, they reported irritation when in contact with water, dust, or sand.

Inheritance

The consanguineous Pakistani family described by Cabral et al. (2012) segregated autosomal recessive peeling skin syndrome.

Mapping

By SNP genomic mapping and microsatellite linkage analysis, Cabral et al. (2012) mapped PSS3 with a lod score of 10.9 to a 16-Mb region on chromosome 19q13 flanked by markers D19S414 and D19S412.

Molecular Genetics

Cabral et al. (2012) performed whole-exome sequencing on a single affected family member with PSS3 and identified a homozygous variant in exon 4 of the CHST8 gene, resulting in an arg227-to-trp (R77W) substitution (610190.0001). The variant was not present in any public databases or in 400 chromosomes from 200 unrelated healthy controls. By Sanger sequencing, Cabral et al. (2012) identified the same mutation in homozygous state in the other 6 affected family members and in heterozygous state in carrier individuals, demonstrating complete cosegregation of the mutation with the phenotype.