INPP5E基因变异所致Joubert综合征一家系的临床及遗传学基因分析

Clinical and genetic analysis of a family with Joubert syndrome caused by INPP5E gene mutation

目的探讨Joubert综合征一家系进行临床表现、磁共振成像(MRI)及遗传学分析,确定家系中的致病基因。方法对2015年10月到2017年10就诊于本院的兄弟2例进行临床特点、影像学检查进行整理,采用目标序列捕获及高通量测序技术,对该家系进行基因检测,应用Sanger测序法对发现的可能的致病突变进行家系成员验证,结合临床症状体征和MRI结果,对该Joubert综合征家系进行临床和分子遗传学分析。结果此家系中2例患儿均表现为语言、运动发育落后,查体肌张力无明显异常,未见特殊面容、体征,2例MRI均表现为小脑下蚓部缺失,四脑室上部呈"蝙蝠翼状"的特殊表现。对该家系进行基因检测发现2例患儿均为INPP5E基因c.1024T>C的纯合突变,确诊为Joubert综合征1型。父母均为此突变杂合子,此突变为一个未见临床报道的新突变。结论 Joubert综合征1型可出现智力、运动发育落后,不伴有视网膜及肾功能异常,综合临床病史、MRI及分子遗传学检测结果可推测INPP5E基因引起c.1024T>C突变是该Joubert综合征家系的致病原因。

Objective To confirm the pathogenicity gene,we analyzed of the clinical,MRI and genetic data of a family which is clinically diagnosed as Joubert syndrome.Method 2 boys of Joubert syndrome boys were enrolled as subject of this study from our hospital's outpatients.We followed the brother's medical history and MRI features from Octomber 2015 to Octomber 2017.Target sequence capture and the hige-thoughout nucleotide sequencing technology were used for the proband and the suffering fetus to find the causative genes and sanger sequencing for the members of the family to check and verify if the inherited mutations are in accordance with the mendelian inheritance.Combining the clinical symptoms and signs with the total testing results,we analyzed the Joubert syndrome family clinically and genetically.Results 2 boys of this family showed language and motor retardation,muscle tension examination showed no abnormalities,no special face and signs.Their magnetic resonance showed"molar tooth sign"in the cerebellar vermis and midbrain.Genetic analysis of the pedigree revealed that both the 2 children had inherited INPP5E genes from their parents.This gene is missense mutation which can change its encoding amino acid.The 2 boys diagnosed Joubert syndrome finally.Conclusion Joubert syndrome type 1 may develop mental and motor retardation without retinal and renal dysfunction.Combined with clinical history,MRI and molecular genetic examination,it can be inferred that the mutation of c.1024T>C caused by INPP5E gene is the causative factor of the Joubert syndrome family.