Proliferative vasculopathy and hydranencephaly–hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism. Issue 3 (3rd March 2018)

• Record Type: Journal Article
• Authors: Radio, Francesca Clementina; Di Meglio, Lavinia; Agolini, Emanuele; Bellacchio, Emanuele; Rinelli, Martina; Toscano, Paolo; Boldrini, Renata; Novelli, Antonio; Di Meglio, Aniello; Dallapiccola, Bruno
• Is Part Of: Molecular genetics & genomic medicine. Volume 6:Issue 3(2018)
• Page Start: 446
• Page End: 451
• Publication Date: 2018-03-03
• Subjects: FLVCR2 -- Fowler syndrome -- hydrocephaly -- multiple pterygium; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.376
• Languages: English
• ISSNs: 2324-9269

Abstract

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. Abstract : 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. Here, 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, supporting the hypothesis of a reduced heme import as the underlying disease's mechanism.