Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis


Lefevre C., Bouadjar B., Karaduman A., Jobard F., Saker S., Ozguc M., ...More

HUMAN MOLECULAR GENETICS, vol.13, no.20, pp.2473-2482, 2004 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 20
  • Publication Date: 2004
  • Doi Number: 10.1093/hmg/ddh263
  • Journal Name: HUMAN MOLECULAR GENETICS
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.2473-2482

Abstract

We report the genomic localization by homozygosity mapping and the identification of a gene for a new form of non-syndromic autosomal recessive congenital ichthyosis. The phenotype usually presents as non-bullous congenital ichthyosiform erythroderma with fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. A few patients presented a more generalized lamellar ichthyosis. Palmoplantar keratoderma was present in all cases, whereas only 60% of the patients were born as collodion babies. Six homozygous mutations including one nonsense and five missense mutations were identified in a new gene, ichthyin, on chromosome 5q33 in 23 patients from 14 consanguineous families from Algeria, Colombia, Syria and Turkey. Ichthyin encodes a protein with several transmembrane domains which belongs to a new family of proteins of unknown function localized in the plasma membrane (PFAM: DUF803), with homologies to both transporters and G-protein coupled receptors. This family includes NIPA1, in which a mutation was recently described in a dominant form of spastic paraplegia (SPG6). We propose that ichthyin and NIPA1 are membrane receptors for ligands (trioxilins A3 and B3) from the hepoxilin pathway.