title: Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D-bifunctional protein deficiency.
abstract: Prenatal diagnosis was requested for a couple with a previous child affected by the peroxisomal disorder D-bifunctional protein deficiency. Prior analysis of the D-bifunctional protein cDNA sequence from the propositus had shown that it was missing 22 bp. This was subsequently attributed to a point mutation in the intron 5 donor site (IVS5 + 1G>C) of the D-bifunctional protein gene. Consistent with parental consanguinity, the patient was shown to be homozygous for this mutation, which is associated with loss of a Hph 1 restriction site in the genomic sequence. Prenatal testing of the fetus using genomic DNA isolated from uncultured amniocytes indicated that both alleles of the D-bifunctional protein had the IVS5 + 1G>C substitution. The peroxisomal defect was later confirmed biochemically using cultured amniocytes, which were found to have elevated levels of very long chain fatty acids (VLCFA). This is the first report of prenatal diagnosis of D-bifunctional protein deficiency using molecular analysis of genomic DNA.
authors.affiliation: Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia. barbara.paton@adelaide.edu.au
authors.forename: B C
authors.initials: BC
authors.lastname: Paton
authors.forename: P B
authors.initials: PB
authors.lastname: Solly
authors.forename: P V
authors.initials: PV
authors.lastname: Nelson
authors.forename: A N
authors.initials: AN
authors.lastname: Pollard
authors.forename: P C
authors.initials: PC
authors.lastname: Sharp
authors.forename: M J
authors.initials: MJ
authors.lastname: Fietz
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000653:Amniotic Fluid / Q000166:cytology; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis*; D004746:Enoyl-CoA Hydratase; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency* / Q000235:genetics; D018598:Minisatellite Repeats; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; D004247:DNA; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase