一个先天性小眼畸形家系的全外显子组测序分析及产前诊断

Whole exome sequencing analysis and prenatal diagnosis for a Chinese pedigree affected with microphthalmia

目的分析1个先天性小眼畸形家系的临床表型及遗传学病因。方法应用高通量测序技术对先证者及其父母进行全外显子组测序,筛选候选致病位点,对其家系进行Sanger测序验证,并通过羊水穿刺和Sanger测序为先证者母亲提供产前诊断。结果全外显子组测序和Sanger测序发现家系中的3例患者均携带OTX2基因c.289C>T(p.R97*)杂合变异,先证者母亲亦携带该变异,但无小眼畸形。先证者的父亲、舅母和胎儿未携带上述变异。结论OTX2基因c.289C>T(p.R97*)杂合变异很可能是该家系的发病原因。上述诊断将有助于该家系的遗传咨询和产前诊断。

Objective To analyze clinical features and genetic cause for a Chinese pedigree affected with microphthalmia.Methods The proband and his parents were subjected to whole exome sequencing(WES)to identify potential pathogenic variants.Sanger sequencing was carried out to confirm the result of WES in available members from the pedigree.Prenatal diagnosis was provided to the proband’s mother by genetic testing of amnionic DNA.Results A heterozygous nonsense mutation c.289C>T(p.R97*)was identified in the OTX2 gene among three patients from the pedigree by WES.The result was confirmed by Sanger sequencing.The proband’s mother has carried the same mutation but did not have microphthalmia.The proband’s father,aunt and the mother’s fetus did not carry the mutation.Conclusion The c.289C>T(p.R97*)mutation probably underlies the microphthalmia in this pedigree.Above result has facilitated genetic counseling and prenatal diagnosis.