Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach.
BACKGROUND
Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disorder mainly caused by mutations in the nephrin gene (NPHS1). The frequency of this gene is highest in Finland but the condition occurs in all populations, with and without Finnish ancestry. The NPHS1 gene is located in the chromosomal region 19q13.1 and consists of 29 exons.


METHODS
Polymerase chain reaction (PCR), restriction and sequence analyses were used to screen 15 CNF Italian patients for mutations in this gene.


RESULTS
No Italian patients had the typical Finnish mutations, a 2bp deletion in exon 2 (Fin-major) and a nonsense mutation in exon 26 (Fin-minor). We found 13 mutations including deletions, insertions, nonsense and missense mutations. Seven of these have never been described before. We also found one nucleotide change in the promoter region and one common polymorphism. NPHS1 missense mutations were confirmed by analysis of a healthy control population.


CONCLUSIONS
Our study provides further evidence that loss of function of the nephrin gene is the main cause of congenital nephrotic syndrome of the Finnish type in Italian patients.
Gigante
Maddalena
M
Department of Biomedicine, University of Bari, Italy.
Monno
Fausta
F
Roberto
Roberta
R
Laforgia
Nicola
N
Assael
Maurice Barouk
MB
Livolti
Salvatore
S
Caringella
Angela
A
La Manna
Angela
A
Masella
Laura
L
Iolascon
Achille
A
D016022:Case-Control Studies; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland / Q000208:ethnology; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics*; D018570:Risk Assessment
D018389:Codon, Nonsense; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin