高通量测序在一罕见脊柱肋骨发育不全病例诊断中的应用

Application of high-throughput sequencing in the diagnosis of a rare case of spondylocostal dysostosis

目的分析一超声结构异常胎儿可能的致病基因及突变位点,为临床遗传咨询提供指导。方法对一超声检测提示脊柱发育异常的胎儿行医学外显子组测序,采用生物信息学方法针对致病基因突变位点进行氨基酸保守型分析及蛋白二、三级结构预测,鉴定其致病性。结果发现与胎儿临床表现相关的致病基因HES7存在c.674T>C(p.F225S)纯合变异,该位点分别遗传自父母,通过分析预测,变异位点能使得蛋白质二级、三级结构相比原始结构发生较显著变化。结论HES7基因c.674T>C(p.F225S)位点的纯合突变可能是导致胎儿脊柱发育异常的致病因素,与Ⅳ型脊椎肋骨发育不全(SCDO4)疾病的发生相关。

Objective To analyze the possible pathogenic genes and mutation sites of a fetus with abnormal ultrasound structure to provide guidance for clinical genetic counseling.Methods Medical exome sequencing was performed on a fetus with abnormal spine dysplasia detected by ultrasound,and bioinformatics methods were used to conduct amino acid conservative analysis and protein secondary and tertiary structure prediction at the mutation site of the disease-causing gene to identify its pathogenicity.Results The pathogenic gene HES7 and the homozygous variant c.674T>C(p.F225S),which are related to the clinical manifestations of the fetus,were discovered.The locus was inherited from the parents.Through analysis and prediction,the mutation site can make the secondary and tertiary structure of the protein more significant changes than the original structure.Conclusion The homozygous mutation at the c.674T>C(p.F225S)locus of the HES7 gene may be a pathogenic factor leading to fetal spinal dysplasia,and is related to the occurrence of type IV spondylocostal dysostosis(SCDO4)disease.