罕见脑桥小脑发育不全家系临床研究及遗传学分析.docVIP

罕见脑桥小脑发育不全家系临床研究及遗传学分析 第37卷第7期 　安　徽　医　学2016年7月 AnhuiMedicalJournal787 ·临床医学· 潘晴晴　王　玉 　　[摘　要]　目的　通过对一个脑桥小脑发育不全(PCH)家系的临床和基因进行研究,探讨它的临床特点及致病基因。方法　对一个脑桥小脑发育不全的家系成员进行临床资料的收集,绘制遗传系谱图,进行认知、脑电、头颅磁共振及全外显子组测序分析,筛选出相关的基因突变,然后对其进行Sanger测序,进行验证。结果　该家系成员中除先证者及其弟,其他成员没有类似疾患表现。先证者及其弟发病年龄、发病症状及神经系统查体结果相似。全外显子组测序:①未能发现该疾病已知的相关基因突变;②未能筛选出临床表型与遗传方式相匹配的突变基因作Sanger测序;③发现了1个基因突变,符合常染色体隐性遗传,但是否与该疾病相关,有待进一步的研究。结论　脑桥小脑发育不全可能有新的基因表达类型。 [关键词]　脑桥小脑发育不全;全外显子组测序;基因突变doi:10．3969/j．issn．1000-0399．2016．07．001 Aclinicalandgeneticstudyofararepontocerebellarhypoplasiafamily PANQingqing,WANGYu DepartmentofNeurology,theFirstAffiliatedHospitalofAnhuiMedicalUniversity,Hefei230022,China[Abstract]　Objective　Tofurtherexploretheclinicalcharacteristicsandgeneticpathogenesisofpontocerebellarhypoplasia(PCH),aPCHfamilywasstudiedconcerningclinicalandgeneticanalysis．Methods　Theclinicaldataincludingclinicalcharacteristics,cognitivefunc-hand,whole-exomesequencing(WES)wasconductedtoscreenthemutantgenewhichwouldbeonSangersequencingtoclarifywhetherano-memberwasaffectedwithsuchdisease．Theprobandhadclinicalfeaturesconsistentwithhisbrotherinonsetage,clinicalpresentations,neuro-tion,electroencephalogram(EEG),magneticresonanceimaging(MRI)werecollectedandthefamilypedigreetreewasdrawn．Ontheothervelgenemutationcouldbefoundanditsassociationwithclinicalfeatures．Results　Exceptfortheprobandandhisbrother,nootherfamilylogicalexaminations．TheWESrevealedonegenemutationconsistentwithautosomalrecessiveinheritance．Furtherstudyshouldbeconductedtocheckwhetherithadrelationshipwiththedisease．①Wefailedtofindtheknownpathogenicgenes．②WefailedtoselectthegenesmutantwhichwouldbeconsistentwithclinicalphenotypeandinheritancepatternforSangersequencing．③Wefoundamutantgenewhichwascon-sistentwithautosomalrecessiveinheritance,butfurtherstudywasofnecessitytoclarifywhetheritwasthepathogenicgeneofthedis-ease．Conclusion　Thisstudyshowsthattheremaybeanewmutantgeneinpotocerebellarhypoplasia．[Keywords]　Pontocerebellarhypopl