Genotype–phenotype correlations with TGM1: clustering of mutations in the bathing suit ichthyosis and self‐healing collodion baby variants of lamellar ichthyosis
Genotype–phenotype correlations with TGM1: clustering of mutations in the bathing suit ichthyosis and self‐healing collodion baby variants of lamellar ichthyosis
复制标题
与 TGM1 的基因型-表型相关性：泳衣鱼鳞病和层状鱼鳞病的自愈胶棉婴儿变体的突变聚类
DOI：
10.1111/j.1365-2133.2009.09537.x
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发表时间：
2010
影响因子：
10.3
通讯作者：
Alan D. Irvine
中科院分区：
文献类型：
--
作者：
B. C. Hackett;D. Fitzgerald;Rosemarie Watson;F. A. Hol;Alan D. Irvine;Alan D. Irvine
出生时火棉胶膜的存在代表皮肤屏障功能的缺陷，通常是先天性鱼鳞状疾病的初始表现，最常见的是常染色体隐性遗传性先天性鱼鳞病(ARCI)。然而，在10%的新生儿中，会发生自发愈合。ARCI包括广泛的鱼鳞病表型，包括小丑鱼鳞病、板层鱼鳞病(LI)和非大疱性先天性鱼鳞状红皮病(NCIE)。到目前为止，已经确定了7个致病基因和另外两个与ARCI相关的基因。最常见的潜在基因缺陷是转谷氨酰胺酶-1(TGM1)，在30-40%的ARCI病例中发现了该基因的突变。这些病例大多表现为安莉表型(广泛分布的大片棕色板状鳞片)；然而，具有TGM1突变的急性心肌梗死病例可表现出相当大的临床和表型多样性。两个这样定义明确的表型变异是泳衣鱼鳞病(BSI)和自愈性火棉婴儿(SHCB)表型。在这里，我们描述了五名出生时出现火棉胶膜的患者的TGM1基因突变(包括两个新的突变)，其中三人最终发展为特有的BSI表型，两人发展为SHCB表型。这些数据扩展了已知的这些TGM1相关表型的基因型-表型相关性。
The presence of a collodion membrane at birth represents a defect in skin barrier function and is usually the initial presentation of a congenital ichthyosiform disorder, most often autosomal recessive congenital ichthyosis (ARCI). However, in 10% of neonates, spontaneous healing occurs. ARCI embraces a wide range of ichthyosis phenotypes including harlequin ichthyosis, lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). To date, seven causative genes and a further two loci for ARCI have been identified. The most common underlying gene defect is in transglutaminase-1 (TGM1), with mutations in this gene found in 30–40% of cases of ARCI. Most of these cases show an LI phenotype (large brown plate-like scale in a generalized distribution); however, cases of ARCI with TGM1 mutations can display considerable clinical and phenotypic diversity. Two such well-defined phenotypic variants are the bathing suit ichthyosis (BSI) and self-healing collodion baby (SHCB) phenotypes. Here we describe mutations (including two novel mutations) in the TGM1 gene in five patients who presented at birth with a collodion membrane, three of whom eventually developed the characteristic BSI phenotype and two who developed an SHCB phenotype. These data extend the known genotype–phenotype correlations for these TGM1-related phenotypes.