{Reference Type}: Case Reports
{Title}: Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism.
{Author}: Radio FC;Di Meglio L;Agolini E;Bellacchio E;Rinelli M;Toscano P;Boldrini R;Novelli A;Di Meglio A;Dallapiccola B;
{Journal}: Mol Genet Genomic Med
{Volume}: 6
{Issue}: 3
{Year}: 05 2018
{Factor}: 2.473
{DOI}: 10.1002/mgg3.376
{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.<BR>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.<BR>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.<BR>Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.