WNK1新突变致遗传性感觉和自主神经病变Ⅱ型的遗传学分析  

Genetic analysis of hereditary sensory and autonomic neuropathy type Ⅱ caused by a new mutation intheWNKlgeneand literaturereview

作　　者：付玉霞 玉仁尼沙·台外库力 梅玫 袁萍[2] 唐增奇[3] 盛娟[1] FU Yuxia;YURENNISHA·Taiwaikuli;MEI Mei;YUAN Ping;TANG Zengqi;SHENG Juan(Reproductive Medicine Centre,The First People's Hospital of Kashi Prefecture,Kashi,Xinjiang 844000,China;IVF Center,Sun Yat-Sen Memorial Hospital Sun Yat-Sen University,Guangzhou,Guangdong 510030,China;Department of Dermatology,Sun Yat-Sen Memorial Hospital Sun Yat-Sen University,Guangzhou,Guangdong 510030,China)

机构地区：[1]喀什地区第一人民医院生殖医学中心,新疆喀什844000 [2]中山大学孙逸仙纪念医院妇科生殖内分泌专科,广东广州510030 [3]中山大学孙逸仙纪念医院皮肤科,广东广州510030

出　　处：《中国优生与遗传杂志》2024年第7期1416-1421,共6页Chinese Journal of Birth Health & Heredity

基　　金：喀什地区科技项目(KS2022002)。

摘　　要：目的 对一个遗传性感觉和自主神经病变Ⅱ型家系遗传学病因分析。方法 应用全外显子组测序技术对孕妇外周血DNA进行检测,对变异位点进行Sanger验证和生物信息预测,同时通过羊水穿刺对胎儿羊水DNA进行染色体微阵列分析(CMA)及全外显子组测序。结果 孕妇表现为以手指甲脱落开始的双手及双足末端的进行性溃疡性萎缩,痛觉减退,部分脚趾的融合消失。测序示孕妇的WNK1存在c.2965C>T(p.Gln989*)纯合变异,其父母为该变异杂合携带者,突变可导致蛋白C端被截短1646个氨基酸。根据ACMG指南判断为致病性。产前诊断结果示胎儿为WNK1突变携带者。结论 本病例首次在维吾尔族患者上诊断遗传性感觉和自主神经病变Ⅱ型,是由WNK1一个新的纯合无义突变所致,丰富了WNK1变异及其表型数据库,而且是首例进行了产前诊断的病例,在中国人群的第3例报道。Objective To explore the genetic etiology of a pregnant woman with hereditary sensory and autonomic neuropathy type II,providing a basis for prenatal diagnosis.Methods The whole exome sequencing technology to detect peripheral blood DNA of the pregnant woman,Sanger verification and bioinformatics prediction for variant sites are con-ducted.The whole exome sequencing technology was used to detect the maternal peripheral blood DNA.Sanger sequencing verification and bioinformatics prediction for variants are conducted.Meanwhile,chromosome microarray analysis and whole exome sequencing of fetal amniotic fluid sample are performed.Results The pregnant woman presented with progressive ul-cerative atrophy of the fingertips,hands,feet and toes,accompanied by reduced sensation and disappearance of fused toes.The results of sequencing showed that the WNK1 gene of the pregnant woman carried homozygous mutations c.2965C>T(p.Gln989*),and her parents were heterozygous carriers of the mutation.The mutation was predicted to introduce premature stop codons,with deletion of 1646 amino acids from the C terminus of the WNK1 protein,which was evaluated to be patho-genic according to the ACMG guidelines.Prenatal diagnosis showed that the fetus was a carrier of the WNKI gene mutation.Conclusion We diagnosed hereditary sensory and autonomic neuropathy type Ⅱ for the first time in a Uyghur patient caused by novel homozygous nonsense mutations in the WNKI gene,enriching the database of WNKI gene genotypes and their phe-notypes.This is also the first case of prenatal diagnosis reported and the third case reported in the Chinese population.

关 键 词：遗传性感觉和自主神经病变 HSAN-Ⅱ 无义突变 全外显子组测序 WNK1 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]