Wang Yu, Song Hanqing, Yu Lingling, Wu Nan, Zheng Xiaodong, Liang Bo, Wang Peiguang
Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Institute of Dermatology, Anhui Medical University, Hefei, China.
Front Genet. 2022 Sep 9;13:943264. doi: 10.3389/fgene.2022.943264. eCollection 2022.
Netherton syndrome (NS, OMIM #256500) is a rare autosomal recessive disease characterized by a triad of congenital ichthyosiform erythroderma (CIE) or ichthyosis linearis circumflexa (ILC), trichorrhexis invaginata (TI), and atopic predisposition. The disease is caused by a mutation in the gene (serine protease inhibitor of Kazal type 5) encoding LEKTI (lymphoepithelial Kazal type-related inhibitor). We performed whole-exome sequencing on one Chinese NS family and made genotype-phenotype correlation analysis on the patients clinically diagnosed with NS or congenital ichthyosis erythroderma. We identified a novel frameshift mutation c.2474_2475del (p.Glu825Glyfs*2) in the gene. The N-terminal mutations of LEKTI cause a severer phenotype, while the C-terminal mutations of LEKT1 are related to a milder phenotype. Our findings suggest that Netherton syndrome may be underestimated clinically, and our findings further expand the reservoir of mutations in Netherton syndrome.
Netherton综合征（NS，OMIM #256500）是一种罕见的常染色体隐性疾病，其特征为先天性鱼鳞病样红皮病（CIE）或回旋线状鱼鳞病（ILC）、套叠性脆发症（TI）和特应性易感性三联征。该疾病由编码LEKTI（淋巴细胞上皮Kazal型相关抑制剂）的SPINK5基因（Kazal型5丝氨酸蛋白酶抑制剂）突变引起。我们对一个中国NS家系进行了全外显子组测序，并对临床诊断为NS或先天性鱼鳞病样红皮病的患者进行了基因型-表型相关性分析。我们在SPINK5基因中鉴定出一个新的移码突变c.2474_2475del（p.Glu825Glyfs*2）。LEKTI的N端突变导致更严重的表型，而LEKT1的C端突变与较温和的表型相关。我们的研究结果表明，Netherton综合征在临床上可能被低估，我们的研究结果进一步扩大了Netherton综合征中SPINK5突变的库。
