Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism

Francesca Clementina Radio, Lavinia Di Meglio, Emanuele Agolini, Emanuele Bellacchio, Martina Rinelli, Paolo Toscano, Renata Boldrini, Antonio Novelli, Aniello Di Meglio, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.

METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.

RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.

CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalMolecular genetics & genomic medicine
Volume6
Issue number3
DOIs
Publication statusPublished - May 2018

Keywords

  • Alleles
  • Amino Acid Sequence/genetics
  • Fetus/pathology
  • Heme/genetics
  • Humans
  • Hydranencephaly/genetics
  • Hydrocephalus/genetics
  • Membrane Transport Proteins/genetics
  • Mutation
  • Receptors, Virus/genetics
  • Vascular Diseases/genetics

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