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目的:分析并确定Helsmoortel-Van der Aa综合征(HVDAS)患儿的临床及遗传学特征。方法:回顾性收集并分析2018年11月至2022年10月在北京大学第一manbet官网登录 就诊的6例HVDAS患儿及其家系成员临床资料，采用全外显子测序技术对患儿家系进行检测，明确遗传学变异，分析基因型-表型关系。结果:1．临床分析结果：6例患儿中男5例，女1例，就诊年龄11个月17 d至12岁9个月，均表现为发育迟缓/智力障碍；2.遗传学分析结果：6例患儿共发现6种 ADNP变异，包括：1种起始密码子缺失变异c.1_2del，2种无义变异c.1175dup，p.(Tyr392*)与c.2213C>G，p.(Ser738*)，3种移码变异c.2632dup，p.(Ser878Lysfs*3)、c.1695_1696insATGGTATGTATGTATGTATG，p.(Val566Metfs*8)和c.2120_2123del，p.(Asn707Serfs*8)，均为新生变异。经美国医学遗传学与基因组学学会评级为致病性变异。除c.2213C>G，p.(Ser738*)外，其他5种变异均为文献未报道的新变异。 结论:6例HVDAS均具有典型临床表现，并拓宽了小头畸形、高身材的表型谱；发现了6种新生变异，拓展了 ADNP突变谱，为该类家庭后续的产前基因诊断和遗传咨询提供了依据。

Objective:To analyze and determine the clinical and genetic characteristics of children with Helsmoortel-Van der Aa syndrome(HVDAS).Methods:Clinical data of 6 children with HVDAS treated at the First Hospital of Peking University from November 2018 to October 2022 and their family members were collected and analyzed retrospectively.Whole exome sequencing was performed on children and their family members to identify the genetic variants.Genotype and phenotype correlation was analyzed.Results:(1) Clinical analysis results: among the 6 children, there were 5 boys and 1 girl, and their age at diagnosis ranged from 11 months and 17 days to 12 years and 9 months.Six patients all presented with developmental delays/intellectual disabilities; (2) Genetic analysis results: 6 de novo ADNP variants were discovered in 6 children, including 1 initial codon deletion variant c. 1_2del, 2 nonsense variants c. 1175dup, p.(Tyr392*) and c. 2213C>G, p.(Ser738*), and 3 frameshift variants c. 2632dup, p.(Ser878Lysfs*3), c.1695_1696insATGGTATGTATGTATGTATG, p.(Val566Metfs*8) and c. 2120_2123del, p.(Asn707Serfs*8).All variants were classified as pathogenic variants by the American College of Medical Genetics and Genomics.Except the c. 2213C>G, p.(Ser738*), the other 5 variants are all novel variants that have not been reported before. Conclusions:All of the 6 cases of HVDAS showed typical clinical manifestations, and expanded the phenotype spectrum of microcephaly and tall stature.Six de novo mutations were discovered, expanding the ADNP mutation spectrum and providing accurate genetic counseling and prenatal genetic diagnosis of the disease.