Identification of a novelPNPLA1mutation in a Spanish family with autosomal recessive congenital ichthyosis

Funding sources: Ramón Areces Foundation project awarded to A.V. Conflicts of interest: None declared. Dear Editor, The term inherited ichthyosis subsumes numerous clinically and aetiologically heterogeneous cornification disorders with Mendelian inheritance patterns. Prior to January 2012, six genes had been identified as having loss‐of‐function mutations causing autosomal recessive congenital ichthyosis (ARCI): ABCA12,ALOX12B,ALOXE3,CYP4F22,NIPAL4 and TGM1.1 In a study of ALOX12B,ALOXE3,CYP4F22,NIPAL4 and TGM1 performed in 17 ARCI families in Galicia (NW Spain),2 3 about 80% of these families had mutant TGM1 or ALOXE3, while no mutations of NIPAL4,CYP4F22 or ALOX12B were found. We later identified the novel ALOX12B mutation c.1609G>A (p.Val537Met referred to as NP_001130.1) in a family with previously undiagnosed ARCI whose affected members were homozygous for this mutation. In 2012 a new locus of ARCI mutations, in PNPLA1, was published4 and we accordingly investigated the prevalence of PNPLA1 mutations in our series of 18 ARCI families, which constitute 95% of the 19 Galician ARCI families identified to date. We report here our results. The eighth known ARCI gene, CERS3, was identified as such only after completion of the present study.5