Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non-consanguineous family outside the Mediterranean

Abstract

Autosomal recessive congenital ichthyosis (ARCI) embraces a wide range of ichthyosis phenotypes, including harlequin ichthyosis, lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma [ 1 Oji V. Tadini G. Akiyama M. Blanchet Bardon C. Bodemer C. Bourrat E. et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol. 2010; 63: 607-641 Abstract Full Text Full Text PDF PubMed Scopus (504) Google Scholar , 2 Akiyama M. Updated molecular genetics and pathogenesis of ichthiyoses. Nagoya J Med Sci. 2011; 73: 79-90 PubMed Google Scholar ]. To date, seven causative genes for ARCI have been identified [ 1 Oji V. Tadini G. Akiyama M. Blanchet Bardon C. Bodemer C. Bourrat E. et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol. 2010; 63: 607-641 Abstract Full Text Full Text PDF PubMed Scopus (504) Google Scholar , 2 Akiyama M. Updated molecular genetics and pathogenesis of ichthiyoses. Nagoya J Med Sci. 2011; 73: 79-90 PubMed Google Scholar , 3 Grall A. Guaguere E. Planchais S. Grond S. Bourrat E. Hausser I. et al. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet. 2012; 44: 140-147 Crossref PubMed Scopus (172) Google Scholar ]. CYP4F22 is a causative gene in LI, and it encodes a cytochrome P450, family F polypeptide 2 homolog of leukotriene B4-omega-hydroxylase (CYP4F22). CYP4F22 is thought to be an orphan CYP, because it is not known to have a function [ [4] Kumar S. Molecular modeling and identification of substrate binding site of orphan human cytochrome P450 4F22. Bioinformation. 2011; 7: 207-210 Crossref PubMed Google Scholar ]. However, in silico analysis of CYP4F22 molecular structure recently revealed putative substrate-binding regions (SBR)s [ [4] Kumar S. Molecular modeling and identification of substrate binding site of orphan human cytochrome P450 4F22. Bioinformation. 2011; 7: 207-210 Crossref PubMed Google Scholar ]. LI, which is caused by CYP4F22 mutations is very rare, with only 2 reports found in the literature; these describe homozygous mutations from consanguineous families in the Mediterranean area [ 5 Lefevre C. Bouadjar B. Ferrand V. Tadini G. Megarbane A. Lathrop M. et al. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet. 2006; 15: 767-776 Crossref PubMed Scopus (164) Google Scholar , 6 Lugassy J. Hennies H.C. Indelman M. Khamaysi Z. Bergman R. Sprecher E. Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch Dermatol Res. 2008; 300: 81-85 Crossref PubMed Scopus (27) Google Scholar ]. Here we describe an LI patient with compound heterozygous CYP4F22 mutations including a novel frameshift mutation in a non-consanguineous family outside the Mediterranean area, and we suggest possible genotype/phenotype correlations in CYP4F22 mutations.