摘要
目的探讨20个希特林缺陷病家系SLC25A13基因的突变特点以及产前诊断的可行性。方法通过高频突变筛查结合直接测序的技术对20例先证者及其父母进行SLC25A13基因突变分析。在确定每个家系基因型后，为先证者母亲再次妊娠的胎儿提供遗传咨询并进行产前诊断。结果20个希特林缺陷病先证者均检出SLC25A13双等位基因致病性突变，共发现10种致病突变类型，包括3种缺失突变：c．851de14、C.1092_1095delT和c．495delA；2种剪接位点突变：IVS6＋5G〉A和IVS11＋1G〉A；2种无义突变：C．775C〉T（P．Q259X）和C．72T〉A（P．Y24X）；1种重复突变：C．1638_1660dup；1种插入突变：IVS16ins3kb；1种错义突变．c．1775A〉C（P．Q592P）。20个家系共行24次产前诊断。其中8例胎儿基因型正常，11例为SLC25A13基因突变携带者，5例为SLC25A13双等位基因突变。2例c．851de14／c．851de14纯合突变胎儿的父母选择继续妊娠，其余3例双等位基因突变胎儿的父母选择终止妊娠。结论对希特林缺陷病家系进行SLC25A13基因突变分析，可以为先证者确诊、受影响家庭的遗传咨询和下一胎产前诊断提供实验依据，有效降低缺陷患儿再发风险。
Objective To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them. Methods The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies. Results Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions （c. 851de14, c. 1092_1095delT, and c. 495delA）, two splice-site mutations （IVS6＋5G〉A and IVSll＋IG〉A）, two nonsense mutations （c. 775C〉T （p. Q259X） and c. 72T〉A （p. Y24X））, one duplication mutation （c. 1638_1660dup）, one insertion （IVS16ins3kb）, and one missense mutation （c. 1775A〉C （p. Q592P））. Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c. 851de14 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated. Conclusion Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.
作者
史珊珊
汤小湄
施资坚
查庆兵
程映
张占会
肖小敏
杨艳东
宋元宗
Shi Shanshan, Tang Xiaomei, Shi Zijian , Zha Qingbing , Cheng Ying , Zhang Zhanhui , Xiao Xiaomin , gang Yandong , Song Yuanzong(Department of Fetal Medicine;Department of Gynecology and Obstetrics ; Department of Pediatrics ; Central Laboratory ; the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, Chin)
出处
《中华医学遗传学杂志》
CAS
CSCD
2018年第4期475-479,共5页
Chinese Journal of Medical Genetics
