title: Prenatal diagnosis of carnitine palmitoyltransferase 2 deficiency in chorionic villi: a novel approach.
abstract: 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.
authors.affiliation: Service de Biochimie B, Groupe Hospitalier Necker-Enfants Malades, Paris, France.
authors.forename: Bernadette Chadefaux
authors.initials: BC
authors.lastname: Vekemans
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Joëlle
authors.initials: J
authors.lastname: Aupetit
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Royer
authors.forename: Véronique
authors.initials: V
authors.lastname: Droin
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Laure
authors.initials: L
authors.lastname: Thuillier
mesh_terms: D000328:Adult; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002824:Chorionic Villi / Q000201:enzymology*; D015193:Chorionic Villi Sampling; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D017931:DNA Primers; D004247:DNA; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase