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Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D‐bifunctional protein deficiency
Author(s) -
Paton B. C.,
Solly P. B.,
Nelson P. V.,
Pollard A. N.,
Sharp P. C.,
Fietz M. J.
Publication year - 2002
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.233
Subject(s) - genomic dna , prenatal diagnosis , point mutation , mutation , genetics , phosphofructokinase 2 , biology , peroxisomal disorder , intron , microbiology and biotechnology , gene , fetus , peroxisome , pregnancy
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.