Hennies H C, Küster W, Wiebe V, Krebsová A, Reis A
Institute of Human Genetics, Charité, Humboldt University, Berlin, Germany.
Am J Hum Genet. 1998 May;62(5):1052-61. doi: 10.1086/301818.
Autosomal recessive lamellar ichthyosis is a severe congenital disorder of keratinization, characterized by variable erythema of the whole body surface and by different scaling patterns. Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2. We have now analyzed the genotype/phenotype correlation in a total of 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage to this locus revealed seven different missense mutations, five of these unpublished so far, and one splice mutation. No genotype/phenotype correlation for mutations in the TGM1 gene was found in this group of patients, which included two unrelated patients homozygous for the same mutation. Similarly, no clear difference in the clinical picture was seen between patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications for patients with lamellar ichthyosis shows no consistency and thus indicates that clinical criteria currently in use cannot discriminate between the molecularly different forms of the disease.
常染色体隐性遗传性板层状鱼鳞病是一种严重的先天性角化异常疾病，其特征为全身皮肤表面出现不同程度的红斑及多种鳞屑形态。最近，在编码角质形成细胞转谷氨酰胺酶的TGM1基因中发现了板层状鱼鳞病患者的突变，并且已将第二个基因座定位于2号染色体。我们现已分析了总共14个板层状鱼鳞病家族的基因型/表型相关性。使用TGM1基因区域内的微卫星进行连锁分析证实了遗传异质性。在与TGM1基因不连锁的患者中，排除了在2号染色体上确定的第二个区域以及20号染色体上的另一个候选区域，这也证实了板层状鱼鳞病至少存在三个基因座。对与该基因座连锁的家族中TGM1基因进行序列分析，发现了七个不同的错义突变，其中五个迄今尚未发表，还有一个剪接突变。在这组患者中未发现TGM1基因突变与基因型/表型之间的相关性，该组患者包括两名同是同一突变纯合子的无关患者。同样，TGM1基因突变患者与未与TGM1基因座连锁的患者之间在临床表现上也未发现明显差异。对板层状鱼鳞病患者的遗传分类和临床分类进行比较，结果显示不一致，因此表明目前使用的临床标准无法区分该疾病分子形式不同的类型。
