全外显子测序技术鉴定一个常染色体显性遗传性痉挛性截瘫3A型家系ATL1基因突变

Identification of ATL1 gene mutation in an autosomal dominant spastic paraplegia pedigree by whole exome sequencing

目的对一个常染色体显性遗传性痉挛性截瘫家系进行全外显子组测序分析,明确其致病基因突变位点。方法收集一个遗传性痉挛性截瘫家系临床资料,提取先证者及其家系成员gDNA,对先证者进行全外显子测序并锁定候选基因致病位点,采用Sanger测序技术对家系中成员进行候选基因致病位点验证。结果全外显子组测序分析发现先证者ATL1基因第10号外显子存在c.715C> T(p. R239C)杂合突变,已有文献报道该突变引起遗传性痉挛截瘫疾病,经Sanger测序验证,家系中其他患者均存在相同突变,家系中正常成员均未检测到该突变。结论 ATL1基因c.715C> T杂合突变是导致该家系成员发生遗传性痉挛截瘫的致病突变,明确致病突变将有助于该家系的遗传咨询和产前诊断。

Objective To identify the pathogenic mutation in a Chinese family with autosomal dominant spastic paraplegia.Methods The clinical data of a family with hereditary spastic paraplegia was collected.The genomic DNA of the proband and his family members was extracted.The whole exon sequencing was performed to detect the proband and identify the candidate gene pathogenic sites.Sanger sequencing technology was used to identify the candidate gene pathogenic sites.Results Results of the whole exome sequencing showed that there was a heterozygous mutation c.715 C>T(p.R239C)in exon 10 of ATL1 gene in the proband,which was reported to cause hereditary spastic paraplegia.Sanger sequencing revealed the same mutation existed in other patients in this family,but this mutation was not detected in the normal members in this family.Conclusion The c.715C>T heterozygous mutation of ATL1 gene is the pathogenic mutation of hereditary spastic paraplegia in this family,and identification of this pathogenic mutation will be helpful for genetic counseling and prenatal diagnosis of this family.