A Disease-Causing Novel Missense Mutation in the ST14 Gene Underlies Autosomal Recessive Ichthyosis with Hypotrichosis Syndrome in a Consanguineous Family

The study investigated the genetic cause of autosomal recessive ichthyosis with hypotrichosis (ARIH) syndrome in a large consanguineous Pakistani family. Using homozygosity mapping and Sanger sequencing, researchers identified a novel homozygous missense variant (c.1315G>A, p.Gly439Ser) in the ST14 gene, which encodes the matriptase protein. This variant co-segregated with the disease phenotype in all affected family members. Structural analysis indicated that glycine at position 439 is crucial for the protein's normal function. The findings supported this ST14 variant as the cause of ARIH syndrome in this family and expanded the known mutation spectrum of the ST14 gene.