Publications
Detailed Information
Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism
Cited 35 time in
Web of Science
Cited 43 time in Scopus
- Authors
- Issue Date
- 2008-04-21
- Publisher
- National Kidney Foundation, Inc
Elsevier
- Citation
- Am J Kidney Dis 51:834-8,2008
- Keywords
- Focal segmental glomerulosclerosis ; α-actinin 4 ; α-actinin 4 ; germline mosaicism ; collapsing glomerulopathy ; nephrin ; NPHS1 gene
- Abstract
- Mutations in the ACTN4 gene cause focal segmental glomerulosclerosis (FSGS), which shows autosomal dominant inheritance (Online Mendelian Inheritance in Man No. 603278, FSGS1). Most patients with a diagnosis of FSGS1 show a mild to moderate degree of proteinuria during adolescence or later, and some patients gradually progress to end-stage renal disease. Here, we report a familial case of FSGS1 in which 2 affected siblings showed unusual clinical, pathological, and genetic features. Both patients presented with full-blown rapidly progressing nephrotic syndrome in early childhood. Renal pathological findings were of an FSGS collapsing variant and FSGS not otherwise specified. A novel ACTN4 mutation, p.Ser262Phe, was detected in the patients, and their father was found to have a germline mosaicism for the mutation. In addition, these siblings also had a heterozygous p.Thr5Met substitution in NPHS1, which encodes nephrin, although the functional significance of this substitution is unclear. This is the third clinical report of FSGS1 and the first case report of germline mosaicism confirmed in patients with hereditary podocyte disorders. FSGS1 may have widely variable clinical and pathological phenotypes and therefore should be considered in young children with full-blown and rapidly progressing nephrotic syndrome. The possibility of germline mosaicism makes interpretation of molecular diagnoses and genetic counseling more difficult.
- ISSN
- 0272-6386 (print)
1523-6838 (online)
- Language
- English
- Files in This Item:
- There are no files associated with this item.
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.