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.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Sep 10;40(9):1146-1149. doi: 10.3760/cma.j.cn511374-20220927-00649.
To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction.
A 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.
The 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 0.000 4%. 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.
The 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.
探讨一名患有智力障碍和射精功能障碍患者的临床特征及遗传病因。
选取2021年11月18日入住空军军医大学第一附属医院的一名患有智力障碍和射精功能障碍的患者作为研究对象。收集该患者的临床资料。采集患者及其父母的外周静脉血样本。对患者进行全外显子组测序（WES），并通过Sanger测序和生物信息学分析验证候选变异。
该患者为26岁男性，表现为非典型智力障碍和射精功能障碍。WES显示他携带ARID1B基因的杂合变异，即c.5776C>T（p.Arg1926X）。Sanger测序验证其父母均未携带相同变异。该变异已记录于千人基因组、ExAC、gnomAD和ClinVar数据库中。对dbSNP数据库的检索表明该变异的人群频率为0.000 4%。包括Mutation Taster、CADD和MutPred在内的在线软件预测该变异为有害变异。使用Cluster Omega在线软件分析表明变异位点编码的氨基酸在不同物种间高度保守。使用PyMOL软件分析表明该变异可能影响编码蛋白的功能。根据美国医学遗传学与基因组学学会（ACMG）和ClinGen的指南，预测该变异为致病性变异。
ARID1B基因的c.5776C>T（p.Arg1926X）变异可能是该患者智力障碍和射精功能障碍的病因。上述发现拓宽了ARID1B基因变异谱，为该患者的诊断和治疗提供了参考。
