Abstract

Background and objectives Mutations in the TRPC6 gene have been recently identified as the cause of late-onset autosomal-dominant focal segmental glomerulosclerosis (FSGS). To extend the screening, we analyzed TRPC6 in 33 Italian children with sporadic early-onset SRNS and three Italian families with adult-onset FSGS. Design, setting, participants, & measurements TRPC6 mutation analysis was performed through PCR and sequencing. The effects of the detected amino acid substitutions were analyzed by bioinformatics tools and functional in vitro studies. The expression levels of TRPC6 and nephrin proteins were evaluated by confocal microscopy. Results Three heterozygous missense mutations (c.374A>G_p.N125S, c.653A>T_p.H218L, c.2684G>T_p.R895L) were identified. The first new mutation, p.H218L, was found in a 18-year-old boy who presented a severe form of FSGS at the age of 8 years. The second, p.R895L, a new de novo mutation, was identified in a girl with collapsing glomerulosclerosis at the age of 2 years. The former mutation, p.N125S, was found in two siblings with early-onset steroid-resistant nephrotic syndrome (SRNS) at the ages of 4 and 14 years. Renal immunofluorescence revealed upregulated expression of TRPC6 and loss of nephrin in glomeruli. The intracellular calcium concentrations were significantly higher in the cells expressing all mutant TRPC6 channels compared with cells expressing wild-type TRPC6

Autore Pugliese

• Ranieri Elena

Tutti gli autori

• M. Gigante , G. Caridi , E. Montemurno , R. Trunzo , A. Schirinzi , F. Aucella , G. Messina , L. Massella , E. Ranieri , G.M. Ghiggeri , L. Gesualdo

Titolo volume/Rivista

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Anno di pubblicazione

2011

ISSN

1555-9041

ISBN

Non Disponibile

Numero di citazioni Wos

35

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

41

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile