Vekemans Bernadette Chadefaux, Bonnefont Jean-Paul, Aupetit Joëlle, Royer Ghislaine, Droin Véronique, Attié-Bitach Tania, Saudubray Jean-Marie, Thuillier Laure
Service de Biochimie B, Groupe Hospitalier Necker-Enfants Malades, Paris, France.
Prenat Diagn. 2003 Nov;23(11):884-7. doi: 10.1002/pd.713.
Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common autosomal recessive inherited disease of the mitochondrial long-chain fatty acid (LCFA) beta-oxidation, may result in three distinct clinical phenotypes, namely, a mild adult muscular form, a severe infantile hepatocardiomuscular disease, and a neonatal form, which includes dysmorphic features in addition to hepatocardiomuscular symptoms. Both the latter forms are life-threatening diseases, and prenatal diagnosis (PND) can be offered to couples at a one-fourth risk of having an affected child. PND of CPT2 deficiency hitherto relied mostly on mutation detection from fresh chorionic villi (10 weeks' gestation), since CPT2 activity could be assayed on cultured amniocytes only (16-17 weeks' gestation).We devised a CPT2 activity assay from 10 mg of chorionic villi sampling (CVS). Combining this enzymatic assay to haplotype study using polymorphic markers linked to the CPT2 gene, we were able to carry out within 2 days, CPT2 deficiency PND, in two unrelated families, using a CVS performed at the 11th week of gestation.
肉碱棕榈酰转移酶2（CPT2）缺乏症是线粒体长链脂肪酸（LCFA）β氧化最常见的常染色体隐性遗传病，可导致三种不同的临床表型，即轻度成人肌肉型、严重婴儿型肝心肌疾病型和新生儿型，后者除肝心肌症状外还包括畸形特征。后两种类型均为危及生命的疾病，对于生育患病孩子风险为四分之一的夫妇可提供产前诊断（PND）。迄今为止，CPT2缺乏症的PND主要依赖于从新鲜绒毛膜绒毛（妊娠10周）中检测突变，因为CPT2活性只能在培养的羊水细胞（妊娠16 - 17周）中进行检测。我们设计了一种从10毫克绒毛取样（CVS）中检测CPT2活性的方法。将这种酶活性检测与使用与CPT2基因连锁的多态性标记进行单倍型研究相结合，我们能够在两天内，对两个无亲缘关系的家庭，利用妊娠第11周进行的CVS完成CPT2缺乏症的PND。
