30例丙酸血症PCCA和PCCB基因遗传变异分析及产前诊断  

Genetic variation and prenatal diagnosis of PCCA and PCCB genes in 30 cases of propionate acidemia

作　　者：朱朝锋[1] 孔祥东[1] ZHU Chaofeng;KONG Xiangdong(Genetic and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,河南郑州450052

出　　处：《中国优生与遗传杂志》2024年第12期2564-2569,共6页Chinese Journal of Birth Health & Heredity

基　　金：国家重点研发计划(2018YFC1002206-2)

摘　　要：目的对30例丙酸血症患者PCCA和PCCB基因进行遗传变异分析,并对其中26个患儿家庭进行产前诊断,为家系遗传咨询及产前诊断提供依据。方法回顾性分析来郑州大学第一附属医院遗传与产前诊断中心就诊的丙酸血症患儿生育史家庭的基因变异信息,其中26个患儿家庭再次妊娠后抽取胎儿羊水或绒毛样本,针对先证者携带的致病性变异对胎儿进行基因诊断。结果30例丙酸血症患儿家系中17例PCCA家系共计检出23种变异,c.2002G>A、c.1850T>C和c.1268C>T较为常见,分别占比26.5%(9/34等位基因)、8.8%(3/34等位基因)和5.9%(2/34等位基因)。13例PCCB家系中共有16种变异,c.1087T>C、c.1228C>T、c.1316A>G和c.838dupC合计占比53.8%(14/26等位基因)。15个变异为首次报道的新变异。变异类型中错义变异分别占比64.7%和69.2%。26个患儿家庭(14例PCCA、12例PCCB)产前诊断结果显示胎儿为患者5例(19.2%),携带者11例(42.3%),未携带者10例(38.5%)。结论30例丙酸血症患者中大部分致病性变异为错义变异,其中PCCA基因c.2002G>A、PCCB基因c.1087T>C和c.838dupC较为常见。产前诊断可有效预防丙酸血症患儿出生。本研究通过回顾性分析30例丙酸血症患者的遗传变异信息并进行产前诊断,为进一步研究疾病发病机制和预防治疗奠定了基础。Objective To analyze the genetic variation of PCCA and PCCB genes in 30 patients with propionic acidemia and to perform prenatal diagnosis in 26 of these families to provide a basis for family genetic counseling and prenatal diagnosis.Methods The genetic variation information of the families with propionic acidemia children who came to The First Affiliated Hospital of Zhengzhou University was retrospectively analyzed.Among them,fetal amniotic fluid or chorionic villus samples were collected during the second pregnancy of 26 families of children with propionic acidemia,and genetic diagnosis of the fetus was performed for the pathogenic variation carried by the proband.Results A total of 30 families with propionate acidemia were collected and prenatal diagnosis was performed.In 17 families with mutations in the PCCA gene,23 variants were detected.The most common variants were c.2002G>A(detected in 26.5%of alleles,9/34 alleles),c.1850T>C(8.8%,3/34 alleles),and c.1268C>T(5.9%,2/34 alleles).In 13 families with PCCB gene mutations,16 variants were identified,with c.1087T>C,c.1228C>T,c.1316A>G,and c.838dupC accounting for 53.8%of alleles(14/26 alleles).Fifteen of the variants found were novel.Missense mutations were the predominant type,accounting for 64.7%in PCCA families and 69.2%in PCCB families.The results of prenatal diagnosis for 26 families(14 with PCCA mutations and 12 with PCCB)showed that the fetuses were affected in 4 cases(15.4%),carriers in 12 cases(46.2%),and non-carriers in 10 cases(38.5%).Conclusion Most of the pathogenic mutations in 30 patients with propionic acidemia were missense mutations,with c.2002G>A in the PCCA gene and c.1087T>C and c.838dupC in the PCCB gene being the most common.Prenatal diagnosis can effectively prevent the birth of children with propionic acidemia.This study retrospectively analyzed the genetic variation information of 30 patients with propionic acidemia and performed prenatal diagnosis for high-risk fetuses,laying a foundation for further research on the pathogenesis,preve

关 键 词：丙酸血症 PCCA PCCB 遗传变异谱 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]