MUTATIONS IN THE GENE FOR TRANSGLUTAMINASE-1 IN AUTOSOMAL RECESSIVE LAMELLAR ICHTHYOSIS
MUTATIONS IN THE GENE FOR TRANSGLUTAMINASE-1 IN AUTOSOMAL RECESSIVE LAMELLAR ICHTHYOSIS
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DOI：
10.1038/ng0395-279
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发表时间：
1995-03-01
期刊：
影响因子：
30.8
通讯作者：
BALE, SK
中科院分区：
文献类型：
--
作者：
RUSSELL, LJ;DIGIOVANNA, JJ;BALE, SK
我们最近将严重常染色体隐性板层状鱼鳞病（LI）的疾病位点定位到染色体14q11上，并发现与编码谷氨酰胺转酶1的基因TGM1有完全的联系。我们现在已经在连锁研究中使用的两个多重Li家族中确定了TGM1的点突变。每一个核苷酸的变化都会导致基因外显子3中相邻的两个精氨酸残基中的一个发生非保守的组氨酸取代（Arg141His, Arg142His）。在转谷氨酰胺酶家族中，这些精氨酸在远离酶的催化位点的保守区域内是不变的。我们假设这些突变对交联的形成产生不利影响，交联是形成角质细胞包膜和正常皮肤角质层所必需的。
We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex Li families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin.