两个新生儿枫糖尿病家系的遗传学分析  

Genetic analysis of two Chinese families with maple syrup urine disease

作　　者：张钏 冯暄[3] 姚立国[3] 郝胜菊 惠玲[3] 陈雪 郑雷[3] 王兴[3] 张庆华[3] 曹宗富[1,2] Zhang Chuan;Feng Xuan;Yao Liguo;Hao Shengju;Hui Ling;Chen Xue;Zheng Lei;Wang Xing;Zhang Qinghua;Cao Zongfu(National Research Institute for Health and Family Planning,National Human Genetic Resources Center,Beijing 100081,China;Graduate School of Peking Union Medical College,Beijing 100730,China;Gansu Province Maternal Generics Center,Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases,Gansu Provincial Maternity and Child-Care Hospital,Lanzhou,Gansu 730050,China)

机构地区：[1]国家卫生健康委科学技术研究所,国家人类遗传资源中心,北京100081 [2]北京协和医学院研究生院,北京100730 [3]甘肃省医学遣传中心,甘肃省出生缺陷与罕见病临床研究中心,甘肃省妇幼保健院,兰州730050

出　　处：《中华医学遗传学杂志》2022年第7期689-693,共5页Chinese Journal of Medical Genetics

基　　金：国家"十三五"重点专项(2016YFC1000307);兰州市科技计划项目资助(2021-1-182);国家人口与生殖健康科学数据中项目(2005DKA32408);甘肃省出生缺陷与罕见病临床医学研究中心项目(21JR7RA680);甘肃省自然科学基金(21JR1RAO47、18JR3RAO36)。

摘　　要：目的对来自两个枫糖尿病(maple syrup urine disease,MSUD)家系的3例患儿进行分析,明确其遗传学病因。方法用高通量测序法对患儿进行基因变异检测,并用Sanger测序对候选变异进行验证。结果家系1患儿携带BCKDHB基因(NM_000056)c.560G>T(p.Gly187Val)纯合突变,家系2患儿携带BCKDHB基因的复合杂合突变c.197-2A>G(splicing)/c.218delT(p.F74Sfs*4)。其中c.560G>T与c.218delT既往均未见报道。结论上述发现丰富了MSUD致病基因BCKDHB的变异谱。Objective To carry out genetic analysis for 3 children from two Chinese families affected with maple syrup urine disease(MSUD).Methods Target capture-next-generation sequencing and Sanger sequencing were used to detect pathogenic variants associated with MSUD.Results The proband from family 1 was found to harbor homozygous c.560G>T(p.Gly187Val)variant of the BCKDHB gene(NM_000056),whilst the two patients from family 2 were found to harbor compound heterozygous variants c.197-2A>G(splicing)/c.218delT(p.F74Sfs*4)of the BCKDHB gene.Among these,the c.560G>T and c.218delT variants were unreported previously.Conclusion The new variants discovered in this study have expanded the mutational spectrum of the BCKDHB gene.

关 键 词：枫糖尿病 遗传学分析 产前诊断 

分 类 号：R722.1[医药卫生—儿科]