22q11.2微缺失综合征相关致病机制探讨  

Pathogenesis Related to 22q11.2 Deletion Syndrome

作　　者：吴谢东 王国建 黄莎莎[1,2,3,4,5,6] 塞娜[1,2,3,4,5,6] 李晓红 李晓鸽[1,2,3,4,5,6] 韩东一 WU Xiedong;WANG Guojian;HUANG Shasha;SAI Na;LI Xiaohong;LI Xiaoge;HAN Dongyi(Department of Otolaryngology-Head&Neck Surgery,the Sixth Medical Center of PLA General Hospital,Beijing 100853,China;Department of Otolaryngology-Head&Neck Surgery,the fifth Medical Center of PLA General Hospital,Beijing 100853,China;PLA Institute of Otolaryngology,Beijing 100853,China;National Key Lab of Hearing Science,Ministry of Education,Beijing 100853,China;Beijing Key Lab of Hearing Impairment Prevention and Treatment,Beijing 100853,China;Chinese PLA School of Medicien,Beijing,100853,China)

机构地区：[1]中国人民解放军总医院第六医学中心耳鼻咽喉头颈外科医学部,北京100853 [2]中国人民解放军总医院第一医学中心耳鼻咽喉头颈外科,北京100853 [3]解放军耳鼻咽喉研究所,北京100853 [4]聋病教育部重点实验室,北京100853 [5]聋病防治北京市重点实验室,北京100853 [6]解放军总医院研究生院,北京100853

出　　处：《中华耳科学杂志》2023年第3期326-330,共5页Chinese Journal of Otology

基　　金：国家自然科学基金面上项目(82171155);解放军总医院第六医学中心创新培育基金(CXPY202113)。

摘　　要：目的 对一临床表型为双侧全聋、特征性面容、先天性心脏病史先证者行全外显子检测,并完善CNV片段验证,明确致病性染色体变异。方法 采集家系成员临床表型,包括家系成员病史特征、面容特征、体格检查、影像学特征、听力学特征等,对先证者行客观听力检测,包括听性脑干反应骨导阈值,听性脑干反应气导阈值,40Hz听觉相关电位,畸变耳声发射等。抽取家系成员静脉血行基因检测。结果 先证者携带22q11.2染色体区域2.77Mb片段缺失,为新发变异,依据ACMG及CNV鉴定标准行致病性分析,明确该变异为该家系致病性突变。结论探究22q11.2微缺失综合征的致病机制,并为该综合征患者提供耳科学诊疗策略。Objective To identify pathogenic chromosomal variation in a proband with syndromic deafness and to improve CNV fragment validation for identifying pathogenic chromosomal variation.Method Whole exon sequencing was performed in a proband patient with bilateral total deafness,characteristic facial features and congenital heart disease.Clinical phenotypes were collected for family members,including medical histories,facial features,physical examination,imaging studies and audiological characteristics.Hearing tests included auditory brainstem responses(thresholds and latencies),40 Hz hearing related potentials and distortion product otoacoustic emissions.Venous blood was collected from family members for genetic testing.Result The proband carried 2.77Mb deletion of the 22q11.2 chromosome region,a new mutation.Pathogenicity analysis according to the ACMG guidelines for CNV identification suggested that the CNV fragment was a pathogenic mutation in this family.Conclusion Assessment in this patient and family members helps understand the pathogenic mechanisms of 22q11.2 deletion syndrome and develop diagnostic and treatment strategies for patients with this condition.

关 键 词：22q11.2 TBX1 CNV 

分 类 号：R764[医药卫生—耳鼻咽喉科]