Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma
Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma
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DOI：
10.1046/j.1365-2133.2001.04037.x
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发表时间：
2001-02-01
影响因子：
10.3
通讯作者：
Shimizu, H
中科院分区：
文献类型：
--
作者：
Akiyama, M;Takizawa, Y;Shimizu, H
我们报告了一名患有非大疱性先天性鱼鳞病样红皮病（NBCIE）的日本男孩的转氨酶（TGase）1基因（TGM 1）的新突变。患者在肿胀的皮肤上显示出细小的灰色或浅棕色鳞片。原位TGase活性测定检测到患者表皮中的TGase活性显著降低。电子显微镜显示角质化过程中的表皮细胞包膜不完全增厚。对TGM 1基因的全部外显子和外显子-内含子边界进行测序，结果显示先证者是两个新突变9008 delA和R388 H的复合杂合子。在板层状鱼鳞病中，大多数先前报道的TGM 1突变位于TGase 1分子的中心核心结构域或上游。在本例NBCIE患者中，导致TGase 1肽尾部提前终止密码子的移码突变9008 delA位于肽的β-桶2结构域（C-末端结构域），远离TGase 1分子的活性位点，错义突变R388 H位于核心结构域。
We report novel mutations in the transglutaminase (TGase) 1 gene (TGM1) in a Japanese boy with non-bullous congenital ichthyosiform erythroderma (NBCIE). The patient showed fine, grey or light-brown scales on an erythematous skin. An in situ TGase activity assay detected markedly reduced TGase activity in the patient's epidermis. Electron microscopy revealed incomplete thickening of the cornified cell envelope during keratinization in the epidermis. Sequencing of the entire exons and exon-intron borders of TGM1 revealed that the proband was a compound heterozygote for two novel mutations, 9008delA and R388H. in lamellar ichthyosis, most previously reported TGM1 mutations have been located in the central core domain or upstream of the TGase 1 molecule. In the present NBCIE patient, the frameshift mutation 9008delA resulting in a premature termination codon at the tail of the TGase 1 peptide was in the beta -barrel 2 domain (C-terminal end domain) of the peptide, far from the active sites of the TGase 1 molecule, and the mis-sense mutation R388H was in the core domain.