Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis
Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis
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DOI：
10.1093/hmg/ddh263
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发表时间：
2004-10-15
影响因子：
3.5
通讯作者：
Fischer, J
中科院分区：
文献类型：
--
作者：
Lefèvre, C;Bouadjar, B;Fischer, J
我们报告了一种新的非综合征型常染色体隐性遗传性先天性鱼鳞病的基因组定位。表型通常表现为非大疱性先天性鱼鳞状红皮病，在红皮背景上有细小的白色鳞片；臀部、颈部和腿部有较大的褐色鳞片。少数患者表现为更广泛的板层状鱼鳞病。所有病例都有掌足部角化病，而只有60%的患者出生时就是火棉婴儿。在来自阿尔及利亚、哥伦比亚、叙利亚和土耳其的14个血缘家庭的23例患者中，在染色体5q33上的一个新基因鱼鳞素中发现了6个纯合子突变，包括1个无义突变和5个错义突变。鱼腥草素编码一个具有多个跨膜结构域的蛋白，它属于一个新的蛋白家族，定位于质膜上，功能未知(PFAM：DUF803)，与转运蛋白和G蛋白偶联受体具有同源性。这个家族包括NIPA1，最近描述了一种突变，表现为一种显性形式的痉挛截瘫(SPG6)。我们认为，鱼腥草素和NIPA1是肝素途径的配体(三苯氧胺A3和B3)的膜受体。
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.