A novel mutation in MBTPS2 causes a broad phenotypic spectrum of ichthyosis follicularis, atrichia, and photophobia syndrome in a large Chinese family

BackgroundIchthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare congenital disorder. Missense mutations in the membrane-bound transcription factor protease, site 2 (MBTPS2) gene have recently been identified in patients with IFAP.ObjectiveTo determine whether Chinese patients with IFAP have MBTPS2 mutations.MethodsWe observed a large IFAP pedigree of 5 generations in a Chinese family and performed MBTPS2 molecular analysis.ResultsThe male proband was severely affected. He presented with hyperextensibility of the interphalangeal joints of the fingers in addition to previously reported clinical manifestations. Clinically affected female patients had hairless patches on the scalp, ichthyosiform skin changes, hypotrichosis, hyperkeratosis, nail dystrophy, and brown scaly plaques, some of which were arranged in a linear pattern following the lines of Blaschko. Molecular analysis identified a novel missense mutation in exon 11 and confirmed cosegregation of the missense mutation with the disease in this family.LimitationsIt is unclear whether hyperextensibility of the fingers was nosologically related to IFAP syndrome or was a coincidental finding.ConclusionThis report provides further evidence for the genetic basis of IFAP syndrome and enlarges the phenotypic spectrum and number of MBTPS2 mutations. We confirm that MBTPS2 mutations cause IFAP in patients of Chinese origin.