单纯性巨指（趾）症PIK3CA基因突变位点研究  

PIK3CA mutation analysis in isolated macrodactyly

作　　者：武竞衡[1] 田伟[1] 田光磊[1] 田萌萌[1] 陈山林[1] 田文[1] Wu Jingheng;Tian Wei;Tian Guanglei;Tian Mengmeng;Chen Shanlin;Tian Wen(Departments of Hand Surgery,Belting Jishuitan Hospital,Beijing 100035,China)

机构地区：[1]北京积水潭医院手外科,100035

出　　处：《中华外科杂志》2018年第7期538-542,共5页Chinese Journal of Surgery

基　　金：北京市医管局“青苗”计划专项资助项目（QML20170402）

摘　　要：目的研究单纯性巨指（趾）患者的PIK3CA基因突变位点。 方法前瞻性系统研究2017年5—8月在北京积水潭医院手外科就诊的12例单纯性巨指（趾）患者的临床资料。患者男性6例，女性6例，平均年龄4.5岁。手术中切除单纯性巨指（趾）患者的病变组织，采用改良的Sanger DNA测序方法来检测PIK3CA基因突变。对Sanger测序结果阴性的患者样本采用下一代测序（NGS）。 结果12例患者中，9例经Sanger DNA测序检测到PIK3CA基因突变，突变水平在7%～27%。突变的位点包括p.His1047Arg、p.His1047Leu、p.Glu545Lys和p.Glu542Lys。NGS又发现1例携带p.Glu453Lys的患者。12例患者中，PIK3CA基因突变阳性者10例。在收集的病变组织检查中，脂肪组织中突变率最高（9/9），其次是皮肤和神经组织（5/6）。 结论PIK3CA基因突变率在单纯性巨指（趾）中极高。受累脂肪、神经及皮肤组织均为理想的基因检测组织来源。Sanger测序目标基因片段可经济适用地检测单纯性巨指（趾）基因突变。ObjectiveTo systematically investigate PIK3CA mutations in isolated macrodactyly. MethodsOvergrowth tissues from 12 isolated macrodactyly patients who were treated at Department of Hand Surgery, Beijing Jishuitan Hospital from May to August 2017 were collected during operation.There were 6 male and 6 female patients with average age of 4.5 years. DNA was tested for PIK3CA mutation using a targeted Sanger DNA sequencing method.Samples with negative Sanger result were tested with a next generation DNA sequencing（NGS）panel targeting 47 cancer hotspot genes including PIK3CA. ResultsBy targeted Sanger sequencing, PIK3CA mutations were detected in 9 of the 12 patients, with mutation level ranging from 7% to 27%.The PIK3CA mutations observed were p. His1047Arg, p.His1047Leu, p.Glu545Lys, and p. Glu542Lys.NGS found p. Glu453Lys in one additional patient, allowing the total positive rate to 10/12.All PIK3CA mutations detected in the study were cancer hotspot mutations.Among all tissue types tested, adipose tissue had the highest mutation detection rate（9/9）, followed by nerve（10/12） and skin（10/12）. ConclusionsA high proportion of isolated macrodactyly patients carry a PIK3CA mutation.Adipose, nerve, and skin are ideal tissue resources for PIK3CA mutation detection.Targeted Sanger sequencing with reflex to NGS represents a cost-effective strategy to test PIK3CA mutations in isolated macrodactyly.

关 键 词：足畸形 手畸形 PIK3CA基因 巨指(趾) 

分 类 号：R658.2[医药卫生—外科学]