Two Null Variants Q2417X and R3409X in FLG Gene are Relevant to Ichthyosis Vulgaris in a Chinese Family

Abstract

Ichthyosis vulgaris (IV) is one of the most ordinary hereditary keratinising illness, characterised by scaly, dry skin, and palmoplantar hyperlinearity. The function loss of filaggrin (FLG) gene mutations is considered as the molecular aetiology for IV. In this study the pathogenic variants of a Chinese IV family were explored by exome sequencing and PCR sequencing. Two null heterozygous variants in FLG coexisted in the pedigree, including c.7249C>T (Q2417X) and c.10225C>T (R3409X). The Q2417X variant was only found in the proband and their healthy mother, whereas the R3409X variant was observed in the other affected family members. The proband with Q2417X showed a much more severe phenotype than the patients with R3409X did, but their mother with Q2417X presented no clinic symptoms. The results strongly support that IV is a semidominant keratinising disorder that involved hereditary and environmental risk aspects and expanded the FLG variants spectrum in Asian populations.