摘要
目的诊断Joubert综合征致病基因。方法应用高通量基因捕获技术对曾怀过Joubert综合征胎儿的夫妻进行基因筛查,并采用荧光定量PCR和Sanger测序法对疑似突变进行验证。从生物学意义、遗传学意义及临床特征吻合度三方面预测新突变的致病性。结果夫妻均为表型正常的Joubert综合征6型AHI1致病基因携带者。妻子为AHI1基因(NM-017651.4)Ex5-6del杂合突变,丈夫为AHI1基因c.1799-1802delAACA杂合突变。AHI1基因是已知的Joubert综合征致病基因,与临床症状相符。这两种突变既往未见数据库及文献收录,按照ACMG解读规则属于致病性突变。结论 AHI1基因(NM-017651.4)是该家系的致病基因,Ex5-6del和c.1799-1802delAACA是AHI1基因新的致病突变,对Joubert综合征诊断及病因筛查具有重要的临床价值。
Objective:To identify causative gene of Joubert syndrome. Methods High-throughput gene capture technology was used to screen causative gene in a couple with Joubert syndrome′s fetal. Suspected mutations were verified with Sanger sequencing or Quantitative fluorescence PCR. Pathogenicity of new mutations were predicted according to ACMG,inheritant mode and clinical phenotype. Results:Couple had normal phenotype but carried heterozygous mutation of AHI1 gene(NM-017651.4),including wife with Ex5-6 del and husband with c.1799-1802 delAACA which had not been reported previously. The two mutations were predicted to be harmful. Conclusion:Ex5-6 del and c.1799-1802 delAACA of AHI1 gene are novel mutations associated with Joubert syndrome type Ⅵ,which may facilitate the genetic diagnosis of Joubert syndrome.
引文
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