In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 6, No. 3 ( 2018-05), p. 446-451
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2324-9269
,
2324-9269
DOI:
10.1002/mgg3.2018.6.issue-3
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2018
ZDB Id:
2734884-2
