一个遗传性痉挛性截瘫家系的全外显子测序分析及产前诊断

Analysis of hereditary spastic paraplegia in a Chinese family by whole exome sequencing

目的对一个常染色体显性遗传性痉挛性截瘫(hereditaryspasticparaplegia,HSP)家系进行全基因组外显子测序分析,找出致病的基因突变位点。方法收集一个遗传性痉挛性截瘫家系,提取先证者、先证者父母的DNA进行全外显子组捕获和测序,锁定候选基因致病位点,针对变异位点在该家系6名患者和9名正常人中进行Sanger测序验证,然后通过羊水穿刺和Sanger测序进一步对1例胎儿羊水进行产前诊断。结果该家系中6例病人均在ATL1基因的同一位点处发生突变(c.715C>T,p. R239C),家系中9例正常人和1例胎儿羊水中均未发现该突变。结论应用全外显子测序技术对遗传性痉挛性截瘫家系进行诊断,明确致病位点,有助于该家系的遗传咨询和产前诊断。

Objectives:To analyze the genetic cause in a family affected with autosomal dominant hereditary spastic paraplegia(HSP)by whole exome sequencing.Methods:The proband with HSP and his parents were investigated by whole exome sequencing(WES)to identify the candidate pathogenic variants,and Sanger sequencing was conducted to confirm the WES result on 6 patients and 9 healthy members in the pedigree.Then,prenatal diagnosis of the fetus was performed by Sanger sequencing after amniocentesis.Results:A heterozygous missense variant c.715 C>T(p.R239 C)of the ATL1 gene was detected in the 6 patients in the pedigree,while 9 healthy members and 1 fetus in the pedigree did not carry the variant.Conclusion:WES could help to identify the genetic etiology of HSP and aid in the genetic counseling and prenatal diagnosis.