COL1A1突变致Van der Hoeve综合征家系的遗传和表型分析并文献复习  

Genetic and Phenotypic analysis of a Family with Van der Hoeve Syndrome Caused by COL1A1 Gene Mutation and Literature Review

作　　者：聂泽群 贺楚峰[1] 吴宏[1] 凌捷 付秦辉 庞博 张帅[1] 陈永嘉 梅凌云[1] Nie Zequn;He Chufeng;Wu Hong;Ling Jie;Fu Qinhui;Pang Bo;Zhang Shuai;Chen Yongjia;Mei Lingyun(Hunan Provincial Key Laboratory of Otolaryngology Institute of Major Diseases,Department of Otolaryngology-Head and Neck Surgery,Xiangya Hospital,Central South University,National Clinical Research Center for Geriatric Disorders(Xiangya Hospital)Changsha,410008,China;不详)

机构地区：[1]中南大学湘雅医院耳鼻咽喉头颈外科耳鼻咽喉重大疾病研究所湖南省重点实验室国家老年疾病临床医学研究中心(湘雅医院),长沙410008 [2]中南大学基础医学院医学机能实验中心

出　　处：《听力学及言语疾病杂志》2024年第5期389-393,共5页Journal of Audiology and Speech Pathology

基　　金：国家自然科学基金面上项目(81873705、82171154);湖南省自然科学基金(2021JJ31084)。

摘　　要：目的对一个常染色体显性遗传的Van der Hoeve综合征家系进行详尽的临床表型分析及基因突变检测,明确该家系的致病基因突变位点及该突变对基因编码的影响。方法对收集到的Van der Hoeve综合征家系进行包括病史、体格检查及辅助检查在内的临床资料的收集及外周血液样本的采集,并对22位家系成员进行外显子组测序以及Sanger测序,利用生物信息学软件分析数据。结果该家系共五代,各代连续发病,且每一代男女均可患病,符合常染色体显性遗传特点。该家系中12例患者均自出生时巩膜即呈蓝色且身材矮小,8例患者有骨折病史,可正常愈合,3例患者考虑有Van der Hoeve综合征所致的听力下降,12例患者的COL1A1基因第17号外显子有一个碱基的缺失(c.1128delT),使第376位后的氨基酸编码改变,在第539位提前结束氨基酸编码,该家系中10例无症状者无此突变。结论该家系患者确定为由COL1A1基因c.1128delT突变导致的Van der Hoeve综合征。Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an autosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examination and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation experiencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

关 键 词：Van der Hoeve综合征 成骨不全 COL1A1基因 基因突变 

分 类 号：R764.431[医药卫生—耳鼻咽喉科]