23个轴前性多指家系临床及基因分析  

Clinical and genetic analysis of 23 families with preaxial polydactyly

作　　者：孙丽颖[1] 黄盈棹 田文[1] 钟文耀 殷悦涵 张楠 杨勇[1] 郭阳[1] 李斌[1] 赵俊会[1] SUN Li-ying;HUANG Ying-zhao;TIAN Wen;ZHONG Wen-yao;YIN Yue-han;ZHANG Nan;YANG Yong;GUO Yang;LI Bin;ZHAO Jun-hui(Department of Hand Surgery,Beijing Jishuitan Hospital,Beijing,100035,China)

机构地区：[1]北京积水潭医院手外科,100035 [2]中国医学科学院北京协和医院骨科,北京100730

出　　处：《中国骨与关节杂志》2020年第11期812-819,共8页Chinese Journal of Bone and Joint

基　　金：国家重点研发计划专项(2016YFC0901500);中国医学科学院罕见病研究中心资助项目(2016ZX310174-4);北京积水潭医院“学科新星”计划专项经费资助(XKXX201818);北京积水潭医院院级基金(ZR-201907,2019-YJ03)。

摘　　要：目的对23个轴前性多指家系进行临床及基因分析,探讨其遗传学病因。方法收集23个轴前性多指患者家系临床资料及外周血样本,进行全外显子基因测序,并对1例伴三节指骨拇指的多并指家系进行基于全外显子组测序的拷贝数变异分析及实时荧光定量PCR检测,结果5例先证者为综合征性轴前性多指,18例为单纯性轴前性多指。共有2例携带致病性突变,其中1例临床诊断为Townes-Brocks综合征的患者携带SALL1基因致病突变[NM_002968.2:c.2712_2715 del(p.Gly906Valfs*59)]1例非综合征性轴前性多指家系携带ZRS区域(7q36.3)杂合性扩增。另有5例分别携带临床意义未明的KCNH1、BMPR1B、CITED2.C2CD3、FANCI基因突变另有2例家系中分别发现恶性高热1型RYR1和家族性乳腺-卵巢癌易感性2型BRCA2基因突变.结论Z/?S区域(7q36.3)杂合性扩增和SALL1突变是轴前性多指致病原因;对于综合征性多指及有条件进行基因分析的非综合征性多指宜进行基因检测,以明确病因、早期发现合并异常,利于日后遗传咨询。Objective To find the genetic basis of 23 families with preaxial polydactyly.Methods Clinical information and peripheral blood samples of 23 families with preaxial polydactyly were collected.Whole exome sequencing was performed.For one patient with copy number variation detected through whole exome sequencing,real time quantitative PCR was used to confirm the copy number variation.Results Five patients were clinically diagnosed as specific syndromes,while 18 patients as isolated preaxial polydactyly.Molecular diagnoses were achieved in 2 families.One patient clinically diagnosed as Townes-Brocks syndrome carried novel pathogenic SALL1 variant[NM_002968.2:c.27122715 del(p.Gly906Valfs*59)].One patient with isolated preaxial polydactyly carried heterozygous microduplication encompassing ZRS(7q36.3).Five patients carried variants of uncertain significance located in KCNH1、BMPR1B,CITED2,C2CD3,and FANCI gene.Incidental findings included RYR1,and BRCA2 variant was observed in two patients.Conclusions Microduplications of ZRS and SALL1 variant are the genetic causes of preaxial polydactyly.Genetic tests should be perfbrmed in patients with preaxial polydactyly especially syndromic form to find the genetic cause and comorbidities,which could help genetic counselling.

关 键 词：多指(趾)畸形 遗传学 全外显子组测序 综合征 Townes-Brocks综合征1型 

分 类 号：R682.1[医药卫生—骨科学]