散发性颅骨锁骨发育不全2例的临床表型及基因变异分析  

Analysis of clinical phenotypes and genetic variants in two children with sporadic cleidocranial dysplasia

作　　者：袁莉敏[1] 刘灵[1] 翟闪闪[1] 李静[1] Yuan Limin;Liu Ling;Zhai Shanshan;Li Jing(Prenatal Diagnosis Center,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第三附属医院产前诊断中心,郑州450052

出　　处：《中华医学遗传学杂志》2023年第3期332-336,共5页Chinese Journal of Medical Genetics

基　　金：河南省科技发展计划(212102310471)。

摘　　要：目的探讨2例散发性颅骨锁骨发育不全(CCD)的临床表型及基因诊断。方法回顾性分析分别在2021年12月16日与2021年12月9日收治于郑州大学第三附属医院的2例CCD的临床资料,并对其进行全外显子组测序(WES)、染色体微阵列分析及拷贝数变异测序。结果胎儿1的产前表型主要包括胎儿颅骨钙化差、顶枕部膨隆、颅骨受压变形、鼻骨缺失等,患儿2在婴幼儿期的表现包括前囟门闭合延迟、反复呼吸道感染、体格发育落后等,影像学提示锁骨发育不全。WES测序发现二者分别携带RUNX2基因c.911_914delinsTTT杂合变异和c.1008delT杂合变异,均为新发变异。结论胎儿锁骨发育不全、颅骨钙化不足、鼻骨缺失是CCD患儿主要的产前超声表现。对于体格发育落后、反复呼吸道感染,锁骨发育不全的婴幼儿也应警惕本病,并通过遗传学检测协助诊断。RUNX 2基因的c.911_914delinsTTT和c.1008del致病变异的发现扩展了RUNX2基因的变异谱,为患儿家庭的遗传咨询和产前诊断奠定了基础。Objective To explore the clinical phenotypes and genetic diagnosis of two cases of sporadic cleidocranial dysplasia.Methods The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16,2021 and December 9,2021 were analyzed retrospectively,and the whole exome sequencing(WES),chromosome microarray analysis and copy number variation sequencing were performed.Results The main ultrasonographic findings of the fetus had included poorly calcified skull bones,budging of parieto-occipital area,compression and deformation of skull,and loss of nasal bone.The infant′s clinical phenotypes included delayed closure of anterior fontanelle,recurrent respiratory tract infection,growth retardation,and clavicular hypoplasia.By WES analysis,case 1 was detected with heterozygous variation of RUNX2 gene c.911_914delinsTTT.Case 2 was detected with heterozygous c.1008delT variant of RUNX2 gene.Both variants were verified by Sanger sequencing to have occurred de novo.Conclusion For sporadic cases featuring cleidocranial dysplasia,prenatal ultrasonography is particularly important.Hypoplastic clavicle,skull calcification and nasal bone absence are the main features.Diagnosis should also be suspected for infants featuring growth retardation,recurrent respiratory tract infections and clavicular dysplasia.Identification of c.911_914delinsTTT and c.1008delT in the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis,and also expanded the mutational spectrum of RUNX2 gene.

关 键 词：颅骨锁骨发育不全 胎儿期 婴幼儿期 基因诊断 RUNX2基因 遗传咨询 

分 类 号：R726.8[医药卫生—儿科]