Biallelic pathogenic variants in the LSS gene cause congenital alopecia-cataract syndrome.

Abstract

Biallelic variants in the LSS gene have been reported in individuals affected by alopecia-intellectual disability syndrome 4, cataract 44, hypotrichosis 14, and palmoplantar keratoderma-congenital alopecia syndrome type 2. The present report described a Chinese girl with congenital alopecia universalis, cataract, esotropia, and nystagmus caused by compound heterozygous variants of c.1025T>G (p.Ile342Ser) and previously unreported c.1011G>A (p.Pro337=) in the LSS gene. Minigene assay confirmed the synonymous variant Pro337= at the edge of exon 9 could produce a novel splice site, leading to a 46-bp insertion of the 5' sequence of the intron 9, likely resulting in a frameshift effect. We consider that the clinical manifestations of this case represent a new type of LSS-related disease, namely congenital alopecia-cataract syndrome (CACS). Our data expand the phenotypic and genetic spectrum of LSS-related diseases.