Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency

Molecular characterization of a novel maternal mutant allele

John D. Isaacs, Harold F. Sims, Cynthia K. Powell, Michael J. Bennett, Daniel Hale, William R. Treem, Arnold W. Strauss

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Acute fatty liver of pregnancy (AFLP) is a devastating late gestational complication with many similarities to the inherited disorders of mitochondrial fatty acid oxidation. We report the molecular defects in a woman with AFLP and her infant who subsequently was diagnosed with trifunctional protein (TFP) deficiency. We used single stranded conformation variance and DNA sequence analyses of the human TFP α-subunit gene, which encodes the long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity, to demonstrate a C to T mutation (C1678T) in exon 16 present on one allele in the mother and the affected infant. This creates a premature termination codon (R524Stop) in the LCHAD domain. Using reverse transcriptase-PCR amplification of the α-subunit mRNA from cultured fibroblasts, we demonstrated that transcripts containing this R524Stop mutation are present at very low levels, presumably because of rapid mRNA degradation. The affected infant also had the common E474Q mutation (nucleotide G1528C) on the second allele. Thus, he is a compound heterozygote. The father and two normal siblings are heterozygous for this E474Q mutation. This initial delineation of the R524Stop mutation provides evidence of the heterogeneity of genetic defects responsible for TFP deficiency and AFLP.

Original languageEnglish (US)
Pages (from-to)393-398
Number of pages6
JournalPediatric Research
Volume40
Issue number3
DOIs
StatePublished - Jan 1 1996

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Fetal Proteins
Alleles
Mothers
3-Hydroxyacyl-CoA Dehydrogenase
Mutation
Mitochondrial Diseases
Genetic Heterogeneity
Nonsense Codon
RNA Stability
Protein Subunits
Heterozygote
Reverse Transcriptase Polymerase Chain Reaction
DNA Sequence Analysis
Fathers
Siblings
Exons
Fatty Acids
Nucleotides
Fibroblasts
Trifunctional Protein Deficiency With Myopathy And Neuropathy

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Isaacs, John D. ; Sims, Harold F. ; Powell, Cynthia K. ; Bennett, Michael J. ; Hale, Daniel ; Treem, William R. ; Strauss, Arnold W. / Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency : Molecular characterization of a novel maternal mutant allele. In: Pediatric Research. 1996 ; Vol. 40, No. 3. pp. 393-398.
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Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency : Molecular characterization of a novel maternal mutant allele. / Isaacs, John D.; Sims, Harold F.; Powell, Cynthia K.; Bennett, Michael J.; Hale, Daniel; Treem, William R.; Strauss, Arnold W.

In: Pediatric Research, Vol. 40, No. 3, 01.01.1996, p. 393-398.

Research output: Contribution to journalArticle

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