Mutations in long-chain 3-hydroxyacyl coenzyme A dehydrogenase are associated with placental maternal floor infarction/massive perivillous fibrin deposition

Adrienne Carruth Griffin, Arnold W. Strauss, Michael J. Bennett, Linda M. Ernst*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Maternal floor infarction/massive perivillous fibrin deposition (MFI/MPVFD) of the placenta has an unclear etiology. The placenta of an 8-month-old child diagnosed with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency reportedly showed MFI, but no further evidence of a direct association between MFI/MPVFD and LCHAD deficiency has been documented. Three cases of MFI/MPVFD were studied. Paraffin blocks of placental tissue were retrieved, tissue scrolls were harvested, and DNA was extracted. The alphasubunit of the mitochondrial trifunctional protein containing the LCHAD coding region (HADHA) was subsequently amplified using specific primer sets and directly sequenced by the dideoxy chain termination method. All 3 placentas demonstrated heterozygous mutations in the HADHA gene. A sample from a 25-4/7 week gestation growth-restricted female infant revealed a heterozygous mutation in exon 11, 1072C>A (glutamine to lysine, Qln358Lys) with a heterozygous sequence difference in the intron following exon 6 (insertion of a T at position +9, +9insT). The 2nd sample from a 32-4/7 week gestation stillborn fetus revealed a heterozygous mutation (+3A>G after exon 3) and a clear homozygous sequence difference in exon 17. The 3rd sample from a 31 weeks gestation infant revealed heterozygosity for the+3A>G mutation after exon 3. All 3 placentas with MFI/MPVFD demonstrated heterozygous mutations in the HADHA gene, and 2 of the 3 placentas had 2 DNA changes. Given a background incidence of heterozygosity for LCHAD mutations of approximately 1 in 220, these findings lend support to the hypothesis that LCHAD mutations may be directly associated with and potentially causative of MFI/MPVFD.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalPediatric and Developmental Pathology
Volume15
Issue number5
DOIs
StatePublished - 2012

Keywords

  • Fatty acid oxidation defects
  • HADHA mutations
  • Long-chain 3-hydroxyacyl coenzyme A deficiency
  • Massive perivillous fibrin deposition
  • Maternal floor infarct

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

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