Phenotypic diversity of the recurrent p.Val379Leu missense mutation of the TGM1 gene

Abstract

Abstract Autosomal recessive congenital ichthyosis type 1 (ARCI1), a clinically heterogeneous group of keratinization disorders, develops due to mutations in the transglutaminase 1 (TGM1) gene. Here we report a Hungarian pedigree affected by the lamellar ichthyosis clinical form of the ARCI1 phenotype. Direct sequencing revealed two recurrent heterozygous mutations: a splice site (c.877-2A > G) and a missense (c.1135G > C, p.Val379Leu) mutation. This splice site mutation is the most frequently observed in ARCI1 worldwide. The missense mutation is relatively rare and has been reported in only 13 Scandinavian patients. Comparison of the clinical phenotypes of our Hungarian patients and the Scandinavian patients demonstrates great phenotypic diversity associated with the p.Val379Leu genotype.