利用高通量测序技术确诊1个CHD7基因突变家系

Identification of 1 family with CHD7 gene mutation by high throughput sequencing

目的本研究旨在采用高通量测序技术确诊明确胎儿畸形原因。方法三维B超显示胎儿唇腭裂、先天性心脏病。孕妇嘴角歪斜,听力异常,手臂缺少支撑力易摔倒。育有一女,症状相似。本研究采用高通量测序技术对胎儿、孕妇及大女儿进行全外显子组测序,并采用Sanger测序进行位点验证。结果在受检者CHD7基因检出c.3082A>G杂合突变,该突变导致CHD7蛋白第1 028位氨基酸残基由Ile变成Val(p.I1028V)。该基因突变会导致CHARGE综合征及伴或不伴嗅觉减退的低促性腺激素性性腺功能减退症5型,均为常染色体显性遗传。受检者临床症状与疾病表型相符。以上结果表明,受检者的CHD7基因c.3082A>G突变是其患病原因。结论 CHARGE综合征及伴或不伴嗅觉减退的低促性腺激素性性腺功能减退症5型临床表型复杂,且与其他疾病有所重叠。采用高通量测序技术可以辅助临床进行诊断,明确疾病及病因。

Objective This study aimed to determine the cause of fetal malformation using high-throughput sequencing. Methods Three-dimensional B-ultrasound showed fetal cleft lip and palate, congenital heart disease. The pregnant woman was of skewed mouth, abnormal hearing, with her arm lacking strength. And her daughter was of the similar symptoms. In this study, high-throughput sequencing was used to sequence the whole exome of fetuses, pregnant women and older daughters, and Sanger sequencing was used for site validation. Results c.3082 AG(NM_017780.3) heterozygous mutation was detected in CHD7 gene. The mutation resulted in the change of Ile to Val in 1 028^(th) amino acid residues of CHD7 protein. This gene mutation caused CHARGE syndrome and hypogonadotrophic hypogonadism type 5 with or without hyposmia, all of which were autosomal dominant. The clinical symptoms of the subject are consistent with the disease phenotype. The above results indicate that the subject's CHD7 gene c.3082 AG mutation is the cause of the disease. Conclusion The clinical phenotype of CHARGE syndrome and Hypogonadotropic hypogonadism 5 with or without hyposmia are complex, and overlap with other disease. High throughput sequencing can help in clinical diagnosis and identify disease and etiologies.