Chao Sheau-Chiou, Tsai Ya-Ming, Lee Julia Yu-Yun
Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan.
J Formos Med Assoc. 2003 Jun;102(6):418-23.
Netherton syndrome (NS) is a severe, autosomal, recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma (CIE), trichorrhexis invaginata (TI) - a distinctive hair-shaft anomaly, and atopic diathesis. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5), the gene that encodes lympho-epithelial Kazal-type-related inhibitor (LEKTI), a recently identified type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. Here we report the mutation analysis of a 7-year-old Taiwanese boy with NS manifesting CIE with pathognomic ichthyosis linearis circumflexa and TI. Direct DNA sequencing of SPINK5 demonstrated a compound heterozygous mutation in the proband, 2260A>T (K754X) in exon 24 and 2468delA in exon 26. The former is a novel mutation and was detected in the mother. The latter mutation was detected in the father and has been previously reported in several European families. Both mutations are expected to result in premature termination codons. Mutation analysis could provide a reliable prenatal diagnosis of this lethal ichthyosis.
Netherton综合征（NS）是一种严重的常染色体隐性鱼鳞病。其特征为先天性鱼鳞病样红皮病（CIE）、套叠性脆发症（TI）——一种独特的毛干异常，以及特应性素质。最近，在丝氨酸蛋白酶抑制剂Kazal型5（SPINK5）中发现了致病突变，该基因编码淋巴细胞上皮Kazal型相关抑制剂（LEKTI），LEKTI是最近发现的一种参与皮肤屏障形成和免疫调节的丝氨酸蛋白酶抑制剂。在此，我们报告了一名患有NS的7岁台湾男孩的突变分析，该男孩表现为CIE伴典型的线状回旋状鱼鳞病和TI。对SPINK5进行直接DNA测序显示，先证者存在复合杂合突变，外显子24中的2260A>T（K754X）和外显子26中的2468delA。前者是一种新突变，在母亲中检测到。后者突变在父亲中检测到，此前已在几个欧洲家族中报道。预计这两种突变都会导致过早出现终止密码子。突变分析可为这种致死性鱼鳞病提供可靠的产前诊断。
