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.
Centre National de Génotypage, Evry, France.
Caroline
C
Lefèvre
Bakar
B
Bouadjar
Aysen
A
Karaduman
Florence
F
Jobard
Safa
S
Saker
Meral
M
Ozguc
Mark
M
Lathrop
Jean-François
JF
Prud'homme
Judith
J
Fischer
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