Molecular prenatal diagnosis in families with fetal mitochondrial trifunctional protein mutations
Molecular prenatal diagnosis in families with fetal mitochondrial trifunctional protein mutations
复制标题
DOI：
10.1067/mpd.2001.111503
复制
发表时间：
2001-03-01
影响因子：
5.1
通讯作者：
Strauss, AW
中科院分区：
文献类型：
--
作者：
Ibdah, JA;Zhao, YW;Strauss, AW
目的：评价线粒体三功能蛋白(TFP)突变家系进行分子产前诊断的可行性，并前瞻性研究胎儿基因型对妊娠结局的影响。TFP催化线粒体长链脂肪酸氧化的最后3步。研究设计：我们对9例妊娠，6个孤立的长链3-羟基酰基辅酶A脱氢酶(LCHAD)缺乏症家族中的8个和一个TFP完全缺乏症家族中的1个进行了分子产前诊断。对7例绒毛标本和2例羊水标本进行分析。结果：9例孕妇均成功地进行了胎儿基因分型。两个胎儿受到影响，两次怀孕都是由家庭决定终止的。另有2例胎儿为正常基因，5例为杂合子。这7次怀孕并不复杂，所有的后代都还活着，看起来很健康。通过分子分析和酶分析确定流产胎儿和新生儿的基因分型。结论：在已知TFP缺陷的家系中，分子产前诊断是可行和有效的指导妊娠处理。携带野生型或杂合型胎儿的TFPα亚基突变杂合子的妇女怀孕并不复杂。
Objectives: To evaluate the feasibility of molecular prenatal diagnosis in families with mitochondrial trifunctional protein (TFP) mutations and prospectively study the effects of fetal genotype on pregnancy outcome. TFP catalyzes the last 3 steps in mitochondrial long-chain fatty acid oxidation.Study design: We performed molecular prenatal diagnosis in 9 pregnancies, 8 in 6 families with isolated long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency and one in a family with complete TFP deficiency. Analyses were performed on chorionic villous samples in 7 pregnancies and on amniocytes in 2.Results: Molecular prenatal diagnosis successfully identified the fetal genotype in all 9 pregnancies. Two fetuses were affected, and both pregnancies were terminated by family decision. Two other fetuses had normal genotype and 5 others were heterozygotes. These 7 pregnancies were uncomplicated, and all the offspring are alive and apparently healthy. Genotypes of the aborted fetuses and neonates were confirmed by molecular analysis and enzymatic assays.Conclusions: Molecular prenatal diagnosis is possible and valid in guiding management of pregnancies in families with known TFP defects. Women heterozygous for TFP alpha -subunit mutations who carry fetuses with wildtype or heterozygous genotypes have uncomplicated pregnancies.