Open AccessProliferative vasculopathy and hydranencephaly–hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism
Author(s) -
Radio Francesca Clementina,
Di Meglio Lavinia,
Agolini Emanuele,
Bellacchio Emanuele,
Rinelli Martina,
Toscano Paolo,
Boldrini Renata,
Novelli Antonio,
Di Meglio Aniello,
Dallapiccola Bruno
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.376
Subject(s) - hydranencephaly , genetics , mechanism (biology) , pathogenesis , gene , mutant , mutation , disease , allele , biology , medicine , pathology , fetus , pregnancy , philosophy , epistemology
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 FLVCR 2 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 FLVCR 2 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 FLVCR 2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR 2 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.