Novel and recurrent PNPLA1 mutations in spanish patients with autosomal recessive congenital ichthyosis; Evidence of a founder effect

Abstract

Autosomal recessive congenital ichthyosis is a group of rare non-syndrome diseases that affect cornifica-tion. PNPLA1 is one of the 12 related genes identified so far. Mutation screening of this gene has resulted in the identification of 13 individuals, from 10 families, who carried 7 different PNPLA1 mutations. These mutations included 2 missense, 2 frame shift and 3 nonsense, 3 of them being novel. One of the identified variants, c.417_418delinsTC, was highly prevalent, as it was found in 6 out of 10 (60%) of our autosomal recessive congenital ichthyosis families with PNPLA1 mutations. Clinical manifestations varied significantly among patients, but altered sweating; erythema, pal-mar hyperlinearity and small whitish scales in flexor-extensor and facial areas were common symptoms. Haplotype analyses of c.417_418delinsTC carriers confirmed the existence of a common ancestor. This study expands the spectrum of the PNPLA1 disease, which causes variants and demonstrates that the c.417_418delinsTC mutation has founder effects in the Spanish population.