一个Meckel-Gruber综合征家系的基因突变分析及产前诊断

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Meckel-Gruber syndrome

目的分析一个Meckel-Gruber综合征家系的致病性变异位点,为家系的遗传咨询及产前诊断提供指导。方法应用全外显子测序的方法对先证者进行基因测序分析,检出的可疑致病变异经PCR扩增后进行Sanger测序家系验证,确定致病性变异后抽取胎盘绒毛组织进行产前诊断。结果先证者携带CEP290基因c.2743G>T(p.E915X)和c.2587-2A>T复合杂合变异,均为未报道的新突变,先证者父母均为杂合携带者,胎儿未携带上述复合杂合突变。结论CEP290基因变异是Meckel-Gruber综合征家系的遗传学病因,为家系遗传咨询和产前诊断提供依据,同时丰富了CEP290基因变异谱。

Objective To carry out genetic testing and prenatal diagnosis for a Chinese couple whomhad conceived two fetuses featuring multiple malformations including polycystic kidney,polydactyly andencephalocele.Methods Following elective abortion,the fetus from the second pregnancy was subjected towhole exome sequencing.Suspected pathogenic variants were verified by Sanger sequencing of the fetus andits parents.Results The fetus was found to harbor compound heterozygous variants of the CEP290 gene,namely c.2743G>T(p.E915X)and c.2587-2A>T,which were respectively inherited from its father andmother,The same variants were not detected among 100 healthy controls nor reported previously.Bioinformatic analysis suggested both variants to be deleterious.The fetus was diagnosed with Meckel-Gruber syndrome,Prenatal diagnosis for the couple during their next pregnancy suggested that the fetus didnot carry the above pathogenic variants.Conclusion The compound heterozygous variants of the CEP290gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus.Above finding hasprovided a basis for genetic counseling and prenatal diagnosis for the couple,and also enriched themutational spectrum of the CEP290 gene.