Uxia Esperón-Moldes, Manuel Ginarte Val, Laura Rodríguez-Pazos, Laura Fachal, José Manuel Azaña, María Barberá Fons, Mónica Viejo Diaz, Ana Vega
DOI: 10.2340/00015555-3227

Autosomal recessive congenital ichthyosis (ARCI) is a group of rare non-syndrome diseases that affect cornification. 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 frame­shift 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 ARCI families with PNPLA1 mutations. Clinical manifestations varied significantly among patients, but altered sweating; erythema, palmar 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.

Due to the growing importance of PNPLA1 mutations in the development of autosomal recessive congenital ichthyosis (ARCI), we decided to sequence this gene in a large, well-characterized cohort of Spanish ARCI patients. The mutational analysis revealed 7 different PNPLA1 mutations, 3 of which were novel, in 13 individuals from 10 families. Interestingly, one of the identified mutations was present in 60% of the families (c.417_418delinsTC; p.Ser140Pro). Haplotype analysis of the c.417_418delinsTC carriers demonstrated that these families are descendants of a recent founder who lived in the XI century, implying that this recurrent mutation has founder effects in the Spanish population.

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