Identification of mutations in FN1 leading to glomerulopathy with fibronectin deposits.
Pediatr Nephrol
; 31(9): 1459-67, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27056061
ABSTRACT
BACKGROUND:
Glomerulopathy with fibronectin deposits (GFND) is a rare autosomal dominant disease characterized by massive fibronectin deposits, leading to end-stage renal failure. Although mutations within the heparin-binding domains of the fibronectin 1 gene (FN1) have been associated with GFND, no mutations have been reported within the integrin-binding domains.METHODS:
In this study, FN1 mutational analysis was conducted in 12 families with GFND. Biochemical and functional features of mutated proteins were examined using recombinant fibronectin fragments encompassing both the integrin- and heparin-binding domains.RESULTS:
We report six FN1 mutations from 12 families with GFND, including five that are novel (p.Pro969Leu, p.Pro1472del, p.Trp1925Cys, p.Lys1953_Ile1961del, and p.Leu1974Pro). p.Pro1472del is localized in the integrin-binding domain of fibronectin, while the others are in heparin-binding domains. We detected p.Tyr973Cys, p.Pro1472del, and p.Leu1974Pro mutations in multiple families, and haplotype analysis implied that p.Pro1472del and p.Leu1974Pro are founder mutations. The protein encoded by the novel integrin-binding domain mutation p.Pro1472del showed decreased cell binding ability via the integrin-binding site. Most affected patients developed urine abnormalities during the first or second decade of life, and some mutation carriers were completely asymptomatic.CONCLUSIONS:
This is the second large-scale analysis of GFND families and the first report of an integrin-binding domain mutation. These findings may help determine the pathogenesis of GFND.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glomerulonefritis Membranoproliferativa
/
Citocinas
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pediatr Nephrol
Asunto de la revista:
NEFROLOGIA
/
PEDIATRIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Japón