title: Mutations in long-chain 3-hydroxyacyl coenzyme a dehydrogenase are associated with placental maternal floor infarction/massive perivillous fibrin deposition.
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 alpha-subunit 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.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Adrienne Carruth
authors: AC
authors: Griffin
authors: Arnold W
authors: AW
authors: Strauss
authors: Michael J
authors: MJ
authors: Bennett
authors: Linda M
authors: LM
authors: Ernst
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D017240:Mitochondrial Myopathies; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D009422:Nervous System Diseases; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D010922:Placenta Diseases / Q000235:genetics*; D011247:Pregnancy; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012206:Rhabdomyolysis; D050497:Stillbirth
chemical_list: D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576205:HADHA protein, human; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D063991:Mitochondrial Trifunctional Protein