中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (5): 397-401.doi: 10.35541/cjd.20200891

• 论著 • 上一篇    下一篇

自我改善型火棉胶鱼鳞病三家系12R-脂氧合酶基因突变分析

杨舟    徐哲    马琳   

  1. 首都医科大学附属北京儿童医院皮肤科  国家儿童医学中心  100045
  • 收稿日期:2020-09-08 修回日期:2020-09-23 发布日期:2021-04-29
  • 通讯作者: 徐哲 E-mail:zhexu_cmu@163.com
  • 基金资助:
    北京市医院管理局儿科学科协同发展中心儿科专项经费（XTZD20180502）

Analysis of 12R-lipoxygenase gene mutations in three families with self-improving collodion ichthyosis

Yang Zhou, Xu Zhe, Ma Lin   

  1. Department of Dermatology, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, China, Beijing 100045, China
  • Received:2020-09-08 Revised:2020-09-23 Published:2021-04-29
  • Contact: Xu Zhe E-mail:zhexu_cmu@163.com
  • Supported by:
    The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority（XTZD20180502）

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摘要： 【摘要】 目的 分析3个自我改善型火棉胶鱼鳞病家系基因突变情况。方法 收集3例自我改善型火棉胶鱼鳞病患者临床资料。提取患者及父母外周血DNA，使用先天性鱼鳞病多基因芯片对患者进行高通量测序，确定致病基因位点后用Sanger测序法对患者及父母DNA双向验证。结果 3例出生时均为火棉胶样儿，2 ~ 4周膜脱落后，均逐渐出现相似的轻度鱼鳞病特征，皮肤干燥，局部细小鳞屑，屈侧易受累，少汗，热不耐受，面颊潮红，轻度掌跖角化或掌纹增多。3例均发现为ALOX12B基因复合杂合突变：例1存在父源c.406_408delGAG、母源c.77T>C突变；例2存在父源c.1013C>T、母源c.1286C>G突变；例3存在父源c.1232T>C、母源c.1440C>A突变。功能预测显示，4个错义突变c.77T>C、c.1286C>G、c.1013C>T、c.1232T> C和1个缺失突变c.406_408delGAG均可能致病，1个无义突变c.1440C>A产生终止密码、编码截短蛋白p.Tyr480Ter，可影响蛋白功能而致病。这6个突变位点既往均未见报道。结论 3例自我改善型火棉胶鱼鳞病患儿均存在ALOX12B基因复合杂合致病突变，每例患儿的2个突变分别来自父母。

关键词: 寻常鳞癣, 自我改善型火棉胶鱼鳞病, 先天性常染色体隐性遗传鱼鳞病, ALOX12B基因, 复合杂合突变

Abstract: 【Abstract】 Objective To analyze gene mutations in 3 families with self-improving collodion ichthyosis. Methods Clinical data were collected from 3 patients with self-improving collodion ichthyosis. DNA was extracted from the peripheral blood of patients and their parents, and high-throughput sequencing was performed in the patients by using a multi-gene panel targeting congenital ichthyosis. After identification of causative gene loci, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents. Results All the 3 patients presented with a collodion-like membrane at birth, which was shed within 2 - 4 weeks after birth, and then they gradually showed similar features of mild ichthyosis, including dry skin, tiny scales at local sites, flexural involvement, mild sweating, heat intolerance, cheek flushing, mild palmoplantar keratosis or palmar hyperlinearity. Compound heterozygous mutations were identified in the ALOX12B gene of the 3 patients, including a paternal mutation c.406_408delGAG and a maternal mutation c.77T>C in case 1, a paternal mutation c.1013C>T and a maternal mutation c.1286C>G in case 2, a paternal mutation c.1232T>C and a maternal mutation c.1440C>A in case 3. Function prediction analysis showed that 4 missense mutations c.77T>C, c.1286C>G, c.1013C>T, c.1232T>C and 1 deletion mutation c.406_408delGAG may exert pathogenic effect, and 1 nonsense mutation c.1440C>A led to the generation of a termination codon encoding a truncated protein p.Tyr480Ter, which may affect the protein function and cause disease. None of the 6 mutation sites had been reported in the past. Conclusion Compound heterozygous pathogenic mutations were identified in the ALOX12B gene of the 3 patients with self-improving collodion ichthyosis, which were inherited from their parents.

Key words: Ichthyosis vulgaris, Self-improving collodion ichthyosis, Autosomal recessive congenital ichthyosis, ALOX12B gene, Compound heterozygous mutations