非典型智力障碍伴射精障碍患者1例的ARID1B基因变异分析  

Analysis of ARID1B gene variant in a patient with mental retardation and ejaculatory dysfunction

作　　者：石润茜 徐盈 张建芳 常媛媛 廖文静 王海旭 Shi Runqian;Xu Ying;Zhang Jianfang;Chang Yuanyuan;Liao Wenjing;Wang Haixu(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Air Force Military Medical University,Xi′an,Shaanxi 710032,China)

机构地区：[1]空军军医大学第一附属医院妇产科,西安710032

出　　处：《中华医学遗传学杂志》2023年第9期1146-1149,共4页Chinese Journal of Medical Genetics

基　　金：陕西省自然科学基础研究计划(2022JQ-977);陕西省重点研发计划(2019ZDLSF01-06);西安市科技计划(20YXYJ0009-7)。

摘　　要：目的探讨1例非典型智力障碍伴射精障碍患者的临床特征与遗传学病因。方法选取2021年11月18日于空军军医大学第一附属医院就诊的1例非典型智力障碍伴射精障碍患者为研究对象。采集患者相关临床资料,抽取患者及其父母外周静脉血样,应用全外显子组测序(WES)对患者进行基因检测,采用Sanger测序进行家系验证,并对候选变异进行致病性分析。结果本研究患者为26岁男性,临床表现为非典型智力障碍伴射精障碍。WES检测结果提示,患者携带ARID1B基因c.5776C>T(p.Arg1926X)杂合变异。经Sanger测序验证,患者父母均未携带该变异,提示该变异为新发变异。ARID1B基因c.5776C>T(p.Arg1926X)变异在1000 Genomes、ExAC、gnomAD及ClinVar等数据库中已见报道;dbSNP数据库检索结果显示,该变异在正常人群中的携带频率为0.0004%;Mutation Taster、CADD及MutPred等在线软件预测结果显示,该变异为有害性变异;Clustal Omega在线软件分析结果显示,该变异位点编码氨基酸在不同物种间高度保守;PyMOL软件分析结果显示,该变异可能影响编码蛋白功能;根据美国医学遗传学与基因组学学会(ACMG)与ClinGen联合制订的相关指南与标准,该变异被判定为致病性变异。结论ARID1B基因c.5776C>T(p.Arg1926X)变异可能是本研究患者智力障碍伴射精障碍的遗传学病因,拓宽了ARID1B基因的变异谱与表型谱,为患者的治疗提供了参考依据。ObjectiveTo explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction.MethodsA patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18,2021 was selected as the study subject.Clinical data of the patient were collected.Peripheral venous blood samples were collected from the patient and his parents.Whole exome sequencing(WES)was carried out for the patient,and the candidate variant was verified by Sanger sequencing and bioinformatic analysis.ResultsThe patient,a 26-year-old male,had manifested atypical mental retardation and ejaculatory dysfunction.WES revealed that he has harbored a heterozygous variant of the ARID1B gene,namely c.5776C>T(p.Arg1926X).Sanger sequencing verified that neither of his parents has carried the same variant.The variant has been recorded in the 1000 Genomes,ExAC,gnomAD and ClinVar databases.A search of the dbSNP database suggested that the variant has a population frequency of 0.0004%.The variant was predicted as deleterious by online software including Mutation Taster,CADD,and MutPred.Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species.Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG)and ClinGen,the variant was predicted to be pathogenic.ConclusionThe c.5776C>T(p.Arg1926X)variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient.Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.

关 键 词：精神发育迟滞 射精障碍 非典型 ARID1B基因 

分 类 号：R749[医药卫生—神经病学与精神病学]