Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D-bifunctional protein deficiency

• Published in: Prenatal diagnosis 2002-01, Vol.22 (1), p.38-41
• Main Authors: Paton, B. C., Solly, P. B., Nelson, P. V., Pollard, A. N., Sharp, P. C., Fietz, M. J.
• Format: Article
• Language: English
• Subjects: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxyacyl CoA Dehydrogenases - deficiency; 3-Hydroxyacyl CoA Dehydrogenases - genetics; Amniotic Fluid - cytology; Biological and medical sciences; Birth control; Cells, Cultured; D-bifunctional protein deficiency; Diseases of mother, fetus and pregnancy; DNA - analysis; Enoyl-CoA Hydratase; Fatty Acids - analysis; Female; Gynecology. Andrology. Obstetrics; Humans; Hydro-Lyases - deficiency; Hydro-Lyases - genetics; Medical sciences; Minisatellite Repeats; Multienzyme Complexes - deficiency; Multienzyme Complexes - genetics; peroxisomal disorder; Peroxisomal Multifunctional Protein-2; peroxisomal β-oxidation defect; peroxisomes; Peroxisomes - chemistry; Polymerase Chain Reaction; Pregnancy; Pregnancy. Fetus. Placenta; prenatal diagnosis; Prenatal Diagnosis - methods; Sterility. Assisted procreation
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.233

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. Copyright © 2002 John Wiley & Sons, Ltd.