SLC25A20基因变异致肉碱-酰基肉碱转位酶缺乏症2例新生儿的临床及遗传学分析  

Clinical and genetic analysis of two pedigree affected with Carnitine-acylcarnitine translocase deficiency due to variant of SLC25A20 gene

作　　者：张庆华[1] 冯暄[1] 王兴[1] 刘芙蓉[1] 周秉博 张钏[1] 王玉佩 石静云[2] 郝胜菊[1] 惠玲 易彬[2] Zhang Qinghua;Feng Xuan;Wang Xing;Liu Furong;Zhou Bingbo;Zhang Chuan;Wang Yupei;Shi Jingyun;Hao Shengju;Hui Ling;Yi Bin(Medical Genetic Center,Gansu Provincial Maternal and Child Health Care Hospital(Gansu Province Central Hospital),Lanzhou,Gansu 730050,China;Neonatal Intensive Care Unit(NICU),Gansu Provincial Maternal and Child Health Care Hospital(Gansu Province Central Hospital),Lanzhou,Gansu 730050,China)

机构地区：[1]甘肃省妇幼保健院(甘肃省中心医院)医学遗传中心,兰州730050 [2]甘肃省妇幼保健院(甘肃省中心医院)新生儿重症救护中心,兰州730050

出　　处：《中华医学遗传学杂志》2024年第4期467-472,共6页Chinese Journal of Medical Genetics

基　　金：甘肃省科技计划(21JR7RA680、20CX4FA003);兰州市人才创新创业项目(2018-RC-95);兰州市科技局计划(2017-4-50)。

摘　　要：目的探讨2例肉碱-酰基肉碱转位酶缺乏症(CACTD)患儿的临床特征与遗传学病因。方法选取2018年1月3日与11月19日于甘肃省妇幼保健院就诊的2例CACTD患儿为研究对象。采集患儿相关临床资料,应用家系全外显子组测序(trio-WES)进行基因检测,对变异位点进行Sanger测序验证与致病性分析。结果2例患儿均为男性,均以低血糖为主要临床表现。Trio-WES与Sanger测序显示患儿1携带SLC25A20基因c.49G>C(p.Gly17Arg)与c.106-2A>G复合杂合变异,分别遗传自其父母;患儿2携带SLC25A20基因c.199-10T>G纯合变异,遗传自其父母;其中c.49G>C(p.Gly17Arg)与c.106-2A>G均未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关标准与指南,c.49G>C(p.Gly17Arg)、c.106-2A>G、c.199-10T>G变异分别评级为可能致病性变异(PM2_supporting+PP3+PM3_strong+PP4)、致病性变异(PVS1+PM2_supporting+PM5+PP3)与致病性变异(PVS1+PM2_supporting+PP3+PP5)。结论结合患儿临床表型与基因型明确诊断为CACTD,为患儿治疗、家系遗传咨询和产前诊断预防提供参考依据。Objective To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency(CACTD).Methods Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19,2018 were selected as the study subjects.Trio-whole exome sequencing(trio-WES)was carried out,and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results Both children were males and had manifested mainly with hypoglycemia.Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene,namely c.49G>C(p.Gly17Arg)and c.106-2A>G,which were inherited from his father and mother,respectively.Child 2 had harbored homozygous c.199-10T>G variants of the SLC25A20 gene,which were inherited from both of his parents.Among these,the c.106-2A>G and c.49G>C variants were unreported previously.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the c.49G>C(p.Gly17Arg),c.106-2A>G,and c.199-10T>G variants were classified as likely pathogenic(PM2_supporting+PP3+PM3_strong+PP4),pathogenic(PVS1+PM2_supporting+PM5+PP3),and pathogenic(PVS1+PM2_supporting+PP3+PP5),respectively.Conclusion Combined with their clinical phenotype and genetic analysis,both children were diagnosed with CACTD.Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

关 键 词：肉碱-酰基肉碱转位酶缺乏症 SLC25A20基因 家系全外显子组测序 新变异 

分 类 号：R722.1[医药卫生—儿科]