Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma

作者：Courcet Jean Benoit; Elalaoui Siham Chafai; Duplomb Laurence; Tajir Mariam; Riviere Jean Baptiste; Thevenon Julien; Gigot Nadege; Marle Nathalie; Aral Bernard; Duffourd Yannis; Sarasin Alain; Naim Valeria; Courcet Degrolard Emilie; Aubriot Lorton Marie Helene; Martin Laurent; Abrid Jamal Eddin; Thauvin Christel; Sefiani Abdelaziz; Vabres Pierre; Faivre Laurence^*

来源：European Journal of Human Genetics, 2015, 23(7): 957-962.

DOI：10.1038/ejhg.2014.213

SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor gene involved in the tumorigenesis of a spectrum of solid cancers. Heterozygous SASH1 variants are known to cause autosomal-dominant dyschromatosis. Homozygosity mapping and whole-exome sequencing were performed in a consanguineous Moroccan family with two affected siblings presenting an unclassified phenotype associating an abnormal pigmentation pattern (hypo-and hyperpigmented macules of the trunk and face and areas of reticular hypo-and hyperpigmentation of the extremities), alopecia, palmoplantar keratoderma, ungueal dystrophy and recurrent spinocellular carcinoma. We identified a homozygous variant in SASH1 (c.1849G>A; p.Glu617Lys) in both affected individuals. Wound-healing assay showed that the patient's fibroblasts were better able than control fibroblasts to migrate. Following the identification of SASH1 heterozygous variants in dyschromatosis, we used reverse phenotyping to show that autosomal-recessive variants of this gene could be responsible for an overlapping but more complex phenotype that affected skin appendages. SASH1 should be added to the list of genes responsible for autosomal-dominant and -recessive genodermatosis, with no phenotype in heterozygous patients in the recessive form, and to the list of genes responsible for a predisposition to skin cancer.

• 出版日期2015-7