【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[NM₀02968.2:c.2712₂715 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 ZRS 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。更多还原

【Abstract】 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[NM₀02968.2: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 performed in patients with preaxial polydactyly especially syndromic form to find the genetic cause and comorbidities,which could help genetic counselling.更多还原