SIX3基因变异导致前脑无裂畸形患儿的遗传学分析

Analysis of a child with holoprosencephaly due to variant of SIX3 gene

目的对1例前脑无裂畸形患儿的SIX3基因进行变异分析,明确其可能的致病原因,为临床诊断提供依据。方法提取DNA样本,应用高通量测序技术对患儿进行基因变异分析,并用Sanger测序进行家系验证。结果MRI提示叶状前脑无裂畸形伴胼胝体部分缺如。基因检测结果显示患儿SIX3存在c.517 C>G(p.His173Asp)杂合变异,父母均为野生型。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,SIX3基因c.517 C>G变异判定为致病变异(PS2+PM1+PM2+PM5+PP3)。结论SIX3基因c.517 C>G变异可能是患儿的致病原因,分子遗传学检查可为临床诊断提供依据。

Objective To explore the genetic basis of a child with holoprosencephaly.Methods Genomic DNA of the child was extracted and subjected to whole exome sequencing.Suspected variant was verified by Sanger sequencing of her family members.Results Cranial MRI suggested lobulated holoprosencephaly with partial absence of corpus callosum.Genetic testing revealed that she has carried a heterozygous c.517C>G(p.His173Asp)variant of the SIX3 gene,for which both of her parents were of wild type.Based on the American College of Medical Genetics and Genomics guidelines,the c.517 C>G variant of SIX3 gene was predicted to be pathogenic(PS2+PM1+PM2+PM5+PP3).Conclusion The SIX3 gene c.517 C>G variant probably underlay the multiple malformations in this child.Above finding has enabled her definite diagnosis.