Cowden综合征1型1例患儿的临床表型与遗传学分析  

Analysis of clinical features and genetic variants in a child with Cowden syndrome 1

作　　者：闫露露[1] 田丽蕴[2] 张玉鑫[1] 刘颖文 曹娟[2] 李冬梅[2] 邹竞慧 李海波 Yan Lulu;Tian Liyun;Zhang Yuxin;Liu Yingwen;Cao Juan;Li Dongmei;Zou Jinghui;Li Haibo(Ningbo Women and Children's Hospital,the Central Laboratory of Birth Defects Prevention and Control,Ningbo,Zhejiang 315012,China;Department of Gynecology,Ningbo Women and Children's Hospital,Ningbo,Zhejiang 315000,China;Department of obstetrics,Ningbo Medical Center Lihuili Hospital,Ningbo,Zhejiang 315000,China)

机构地区：[1]宁波市妇女儿童医院出生缺陷综合防治实验室,浙江315000 [2]宁波市妇女儿童医院胎儿医学门诊,浙江315000 [3]宁波市医疗中心李惠利医院产科,浙江315000

出　　处：《中华医学遗传学杂志》2024年第2期230-233,共4页Chinese Journal of Medical Genetics

基　　金：浙江省医药卫生科技计划(2020KY890);宁波市科技计划(202002N3150、2023Z178);宁波市医疗卫生高端团队重大攻坚项目(2022020405)。

摘　　要：目的探讨1例Cowden综合征1型(CS1)患儿的遗传学原因,明确其致病原因。方法选取2022年8月26日在宁波市妇女儿童医院就诊的1例CS1患儿作为研究对象,收集患儿的临床资料。采集外周血样提取DNA,进行全外显子组测序(WES),并通过Sanger测序技术对候选变异进行验证。结果患儿为13岁男性,表现为智力严重低下,精神异常亢奋、自闭症行为,牙齿稀疏且突出,巨头畸形和阴茎头色素性斑点斑。患儿母亲主要表现为多发处乳头状丘疹,错构瘤形息肉,甲状腺腺瘤和巨头畸形。WES检测结果提示患儿携带PTEN基因c.781C>T(p.Q261*)杂合变异,遗传自母亲。依据美国医学遗传学和基因组学学会指南,c.781C>T变异评判为可能致病性变异(PVS1+PM2Supporting)。结论PTEN基因c.781C>T变异考虑为该CS1患儿及其母亲的致病原因,上述发现有助于对该家系进行遗传咨询。Objective To explore the genetic etiology of a child with Cowden syndrome 1(CS1).Methods A child who had visited the Ningbo Women and Children's Hospital on August 26,2022 was selected as the study subject.Clinical information of the child was collected.Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing.Results The child,a 13-year-old boy,had manifested with severe mental retardation,hyperactivity,autistic behavior,sparse and prominent teeth,macrocephaly,and skin freckles on the penis.His mother had presented with multiple papules,hamartomatous polyps,thyroid adenoma and macrocephaly.WES results revealed that the child has harbored a nonsense c.781C>T(p.Q261*)variant of the PTEN gene,which was inherited from his mother.Based on the guidelines from the American College of Medical Genetics and Genomics,the c.781C>T variant was classified as likely pathogenic(PVS1+PM2_Supporting).Conclusion The c.781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother.Above finding has facilitated genetic counseling for this family.

关 键 词：Cowden综合征1型 PTEN基因 无义变异 全外显子组测序 儿童 

分 类 号：R725.9[医药卫生—儿科]