一个枫糖尿病家系基因突变分析和产前诊断  

Mutation analysis and prenatal diagnosis for a pedigree affected with maple syrup urine disease

作　　者：梅世月[1] 白楠[1] 胡爽 刘宁[1] 赵振华[1] 孔祥东[1] Mei Shiyue , Bai Nan, Hu Shuang , Liu Ning , Zhao Zhenhua , Kong Xiangdong(Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, Chin)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2018年第5期679-682,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1个枫糖尿病（maplesyrup urine disease，MSUD）家系进行致病基因突变分析，明确其遗传学病因。方法应用PCR-Sanger测序方法对先证者BCKDHA和BCKDHB基因的外显子编码区进行序列突变分析。明确患儿致病突变后，先证者母亲于孕12周抽取胎盘绒毛进行产前基因诊断。结果测序结果显示先证者携带BCKDHB基因c．284G〉C（p．Gly95Ala）和c．853C〉T（P．Arg285＊）复合杂合突变；先证者父亲携带c．284G〉C（p．Gly95Ala）杂合突变，母亲携带c．853C〉T（p．Arg285＊）杂合突变。其中c．853C〉T（p．Arg285＊）为已报道的致病突变，c．284G〉C（p．Gly95Ala）为未报道过的新突变。产前诊断结果显示胎儿为c．853C〉T（p．Arg285＊）杂合突变携带者，出生后表型和智力发育正常。结论BCKDHB基因c．284G〉C（p．Gly95Ala）和c．853C〉T（p．Arg285＊）突变为该家系的致病原因，遗传学病因的明确为家系产前诊断提供了依据。Objective To carry out mutation analysis for a pedigree affected with maple syrup urine disease （MSUD）. Methods Clinical data of the prohand was collected. Potential mutations of the BCKDHA and BCKDHB genes were analyzed by PCR and Sanger sequencing. Prenatal diagnosis was provided to a high-risk fetus at 12th gestational week through chorionic villus sampling. Results Two heterozygous mutations c. 284G〉C （p. Gly95Ala） and c. 853C〉T （p. Arg285 ＊ ） of the BCKDHB gene were identified in the proband, which were inherited from his mother and father, respectively. Among these, c. 853C〉T （p. Arg285 ＊ ） was known to be pathogenic, while c. 284G〉C （p. Gly95Ala） was a novel mutation. Prenatal diagnosis showed that the fetus has inherited the c. 284G〉C （p. Gly95Ala） mutation from its mother hut no mutation from its father. After birth, the infant appeared to be healthy. Conclusion The compound heterozygous mutations c. 284G〉C （p. Gly95Ala） and c. 853C〉T （p. Arg285 ＊ ） probably underlie the pathogenesis of MUSD in the prohand. Mutation analysis can facilitate prenatal diagnosis and genetic counseling for the affected families.

关 键 词：枫糖尿病 BCKDHB基因 突变分析 产前诊断 

分 类 号：R440[医药卫生—诊断学] R714.5[医药卫生—临床医学]