一个颅骨锁骨发育不全家系的临床表型及遗传学分析  

Analysis of clinical phenotype and genetic variant in a Chinese pedigree affected with cleidocranial dysplasia

作　　者：陈银花 顾海斌 汤根兄[3] 李荣[1] Chen Yinhua;Gu Haibin;Tang Genxiong;Li Rong(Department of Child Health Care,the Affiliated Children′s Hospital of Nanjing Medical University,Nanjing,Jiangsu 210008,China;Department of Medical Imaging,the Affiliated Children′s Hospital of Nanjing Medical University,Nanjing,Jiangsu 210008,China;Department of Stomatology,the Affiliated Children′s Hospital of Nanjing Medical University,Nanjing,Jiangsu 210008,China)

机构地区：[1]南京医科大学附属儿童医院儿童保健科,南京210008 [2]南京医科大学附属儿童医院影像科,南京210008 [3]南京医科大学附属儿童医院口腔科,南京210008

出　　处：《中华医学遗传学杂志》2022年第11期1247-1251,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨一个疑似颅骨锁骨发育不全(cleidocranial dysplasia,CCD)家系的临床特征和遗传学病因,为遗传咨询和产前诊断提供依据。方法收集8名家系成员的临床信息以及其中6人的外周血样,提取DNA。对先证者以及其他3位患病成员进行全外显子组测序,针对候选变异,在其他2位成员中进行Sanger测序验证。结果该家系4代共22人,其中8人患病,测序检测提示先证者携带RUNX2基因[NM_001024630:c.1268_1277del(p.P425Afs*56)]致病变异,遗传自母亲,其他5名患病个体均携带该变异,而健康成员则未见相同的变异,基因型与表型存在共分离。结论RUNX2基因c.1268_1277del(p.P425Afs*56)变异可能是该CCD家系的遗传学病因,为临床诊治和产前诊断提供了依据。Objective To analyze the clinical features and pathogenic variant in a Chinese pedigree affected with cleidocranial dysplasia(CCD).Methods Clinical data of 8 patients from the pedigree was collected,including physical examination and X-ray images of head,face,spine,limbs,and mouth.Peripheral blood samples were collected from 6 affected members for the extraction of genomic DNA.The proband and other 3 patients were subjected to trio-whole exome sequencing.Candidate variant was verified by Sanger sequencing of the other 2 affected members from the pedigree.Results This pedigree has included 22 members(8 affected)from four generations.Genetic testing revealed that the proband has harbored a novel pathogenic variant of the RUNX2 gene[NM_001024630:c.1268_1277del(p.P425Afs*56)],which was inherited from her mother and carried by all affected members in the pedigree.The same variant was not detected among the unaffected members,suggesting co-segregation with the phenotype.Conclusion The c.1268_1277del(p.P425Afs*56)variant of the RUNX2 gene probably underlay the pathogenesis of CCD in this pedigree.Genetic testing has facilitated the definite diagnosis and enabled prenatal diagnosis.

关 键 词：颅骨锁骨发育不全 RUNX2基因 变异 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]