全基因组外显子测序捕获黏多糖贮积症Ⅶ型的致病基因 GUSB

摘要

目的：鉴定黏多糖贮积症Ⅶ型患者的致病基因，为产前诊断提供新的方法。方法应用全基因外显子组技术捕获该患者致病基因，结合现代生物信息学方法，采用Sanger测序验证基因突变位点是否存在该患者家系成员和健康人基因组内。结果发现该患者基因β‐葡萄糖醛酸酶（G U SB ）（g ．65444706G＞A ）突变，健康人未见该突变，该碱基的突变导致苏氨酸变成丝氨酸，从而导致GUSB活性缺乏或GUSB量的不足。结论基因GUSB （g ．65444706G＞A ）突变是该患者的致病基因，全基因组外显子测序能解决传统定位克隆技术常常面临该病家系患者太少、病例散发、基因位点的异质性、外显不全及候选基因太多等难题，为该病产前诊断提供了新的途径。%Objective To identify the pathogenic gene of the patients with mucopolysaccharidosis Ⅶ (MPSⅦ) to provide a new method for the prenatal diagnosis .Methods The whole genome exome technology was applied to capture the pathogenic gene of the patients ;by combining with the methods of modern bioinformatics ,the Sanger sequencing was used to verify whether the gene mutation locus existing in the genome of the patient′s family mem‐bers or the normal people .Results Theβ‐glucuronidase (GUSB) (g .65444706G> A) gene mutation existed in the patients ,but the normal ones had no this mutation .The mutation of the base caused threonine changibng to azaserine , and thus led to the absence of GUSB activity or the insufficiency of GUSB amount .Conclusion The GUSB gene (g .65444706G>A) mutation is the pathogenic gene in this patients .The whole genome exome sequencing can solve many problems of the traditional positional cloning technology ,such as too few of the patients in the family members of this disease ,sporadic cases ,heterogeneity of the genetic locus ,incomplete exon and too many candidate genes , which provides new approach in the prenatal diagnosis of this disease .