FAH基因新变异所致酪氨酸血症Ⅰ型(急性型)患儿1例的临床特征及遗传学分析  

Clinical features and genetic analysis of a child with acute form of Tyrosinemia type Ⅰ due to a novel variant of FAHgene

作　　者：张庆华[1] 张钏[1] 王玉佩 王卫凯[2] 徐瑞峰[2] 惠玲 冯暄[1] 王兴[1] 郑雷[1] 周秉博 江燕[2] 郝胜菊[1] Zhang Qinghua;Zhang Chuan;Wang Yupei;Wang Weikai;Xu Ruifeng;Hui Ling;Feng Xuan;Wang Xing;Zheng Lei;Zhou Binbo;Jiang Yan;Hao Shengju(Medical Genetics Center,Gansu Provincial Maternal and Child Health Care Hospital,Lanzhou,Gansu 730050,China;Pediatric Intensive Care Unit(PICU),Gansu Provincial Maternal and Child Health Care Hospital,Lanzhou,Gansu 730050,China)

机构地区：[1]甘肃省妇幼保健院医学遗传中心,兰州730050 [2]甘肃省妇幼保健院儿童重症救护中心,兰州730050

出　　处：《中华医学遗传学杂志》2023年第2期171-176,共6页Chinese Journal of Medical Genetics

基　　金：甘肃省科技计划项目(21JR7RA680);甘肃省卫生健康行业科研计划项目(GSWSKY2021-001);兰州市人才创新创业项目(2018-RC-95)。

摘　　要：目的探讨1例酪氨酸血症Ⅰ型(TYRSN1)(急性型)患儿的临床表型和遗传学病因。方法选取2020年10月至甘肃省妇幼保健院就诊的1例TYRSN1(急性型)患儿为研究对象。采用血串联质谱和尿气相色谱质谱法对患儿进行遗传代谢病检测,同时对其进行全外显子组测序(WES),用Sanger测序对候选变异进行家系验证。结果患儿表现为腹胀、肝脏肿大、贫血以及凝血功能异常等,血串联质谱和尿气相色谱质谱分析发现其酪氨酸与琥珀酰丙酮等指标增高,WES检测结果提示患儿携带FAH基因c.1062+5G>A和c.943T>C(p.Cys315Arg)复合杂合变异,Sanger测序结果显示二者分别遗传自其父亲和母亲,其中c.943T>C变异既往未见报道。结论结合其临床表型及基因检测结果,患儿被诊断为TYRSN1(急性型)。FAH基因c.1062+5G>A和c.943T>C(p.Cys315Arg)复合杂合变异为其遗传学病因。上述发现拓展了FAH基因的变异谱,为患儿的诊疗及家系遗传咨询和产前诊断提供了依据。Objective To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I(TYRSN1).Methods A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject.The child was subjected to tandem mass spectrometry(MS-MS)and urine gas chromatography-mass spectrometry(GCMS)for the detection of inherited metabolic disorders,in addition with whole exome sequencing(WES).Candidate variants were validated by Sanger sequencing.ResultssThe child's clinical features included abdominal distension,hepatomegaly,anemia and tendency of bleeding.By mass spectrometry analysis,her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges.WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C(p.Cys315Arg))compound heterozygous variants of the FAH gene,which were inherited from her father and mother,respectively.Among these,the c.943T>C was unreported previously.Conclusion Considering her clinical phenotype and result of genetic testing,the child was diagnosed with TYRSNl(acute type).The compound heterozygous variants of the FAH gene probably underlay the disease in this child.Above finding has further expanded the spectrum of FAH gene variants,and provided a basis for accurate treatment,genetic counseling and prenatal diagnosis for her family.

关 键 词：酪氨酸血症Ⅰ型 急性型 FAH基因 全外显子组测序 新变异 

分 类 号：R725.8[医药卫生—儿科]