目的:对1例前脑无裂畸形患儿的n 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。n 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n 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，n SIX3基因c.517 C>G变异判定为致病变异(PS2+PM1+PM2+PM5+PP3)。n 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。n “,”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 then 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 ofn SIX3 gene was predicted to be pathogenic(PS2+ PM1+ PM2+ PM5+ PP3).n Conclusion:The n SIX3 gene c. 517 C>G variant probably underlay the multiple malformations in this child. Above finding has enabled her definite diagnosis.n