一个MAB21L2基因变异所致综合征型小眼畸形家系的遗传学分析及产前诊断

Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with microphthalmia/coloboma and skeletal dysplasia syndrome due to variant of MAB21L2 gene

目的分析一例小眼畸形家系的遗传学病因,为产前诊断提供依据。方法收集患儿的临床资料,采集患儿及其父母、祖父母的外周血样,提取基因组DNA,通过全外显子测序检测基因变异,并用Sanger法进行验证。通过序列分析和PubMed检索预测候选变异的致病性。为患儿母亲提供羊水穿刺,通过Sanger测序进行产前诊断。结果患儿及其父亲均检测到MAB21L2基因c.151C>G(p.R51G)杂合变异,其母亲、祖父母均未检测到该变异。根据美国医学遗传学学会指南并结合其临床表现,判定c.151C>G(p.R51G)为疑似致病变异。结论MAB21L2基因c.151C>G(p.R51G)变异可能是患儿的发病原因,据此可为患儿的母亲提供产前诊断。

Objective To explore the genetic basis for a Chinese pedigree affected with microphthalmia.Methods Clinical data of the proband was collected.Whole exome sequencing(WES)was carried out to screen potential pathogenic variants in the proband.Candidate variant was verified by Sanger sequencing of the proband and his family members.Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis.Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis.Results The proband and his father were found to harbor a heterozygous c.151C>G(p.R51G)variant of the MAB21L2 gene.The same variant was not found in his mother and grandparents.Based on the guidelines of American College of Medical Genetics,the c.151C>G(p.R51G)variant was predicted as likely pathogenic.Conclusion The c.151C>G(p.R51G)variant of the MAB21L2 gene probably underlay the microphthalmia in the proband.Above finding has facilitated prenatal diagnosis for this pedigree.