Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis.
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.
Lefèvre
Caroline
C
Centre National de Génotypage, Evry, France.
Bouadjar
Bakar
B
Karaduman
Aysen
A
Jobard
Florence
F
Saker
Safa
S
Ozguc
Meral
M
Lathrop
Mark
M
Prud'homme
Jean-François
JF
Fischer
Judith
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000208:ethnology / Q000235:genetics*; D017490:Ichthyosis, Lamellar / Q000208:ethnology / Q000235:genetics; D007645:Keratoderma, Palmoplantar / Q000208:ethnology / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics
C499859:NIPAL4 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled