title: NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children.
abstract: Podocin is an integral membrane protein encoded by NPHS2, which is mapped to 1q25-31 and is exclusively expressed in glomerular podocytes. NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset (age less than 6 years) and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent/adult onset form of autosomal recessive familial FSGS with heavy proteinuria. It has been demonstrated that sporadic SRNS and heavy proteinuria are also due to NPHS2 gene mutations. We isolated genomic DNA from 36 Japanese children with chronic renal insufficiency caused by SRNS or heavy proteinuria, and analyzed all eight exons and exon-intron boundaries of NPHS2 using the polymerase chain reaction and direct sequencing. The age at onset of disease was 3.9+/-0.5 years. There were 29 patients with SRNS and 7 with heavy proteinuria without nephrotic syndrome at the onset, but all patients developed chronic renal insufficiency 4.6+/-0.8 years after the onset. A new homozygous missense variant of NPHS2, G34E (G101A) in exon 1, was detected in 1 of 36 patients. However, this homozygous variant was also found in 1 of 44 normal controls, suggesting that the mutation is a polymorphism. Two silent variants (T954C and A1038G) in exon 8 of this gene were also identified in some of the patients and normal controls, indicating that the silent variants are also polymorphisms. There was no significant difference in the genotypic and allelic frequencies of T954C and A1038G polymorphisms between the patients and normal controls. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by sporadic SRNS or heavy proteinuria in Japanese children.
authors.affiliation: Faculty of Health Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Maruyama
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.forename: Akiko
authors.initials: A
authors.lastname: Kitamura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tsukaguchi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yoshiya
authors.forename: Sakurako
authors.initials: S
authors.lastname: Hoshii
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wada
authors.forename: Osamu
authors.initials: O
authors.lastname: Uemura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Satomura
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D004351:Drug Resistance; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics*; D017354:Point Mutation; D011507:Proteinuria / Q000188:drug therapy / Q000235:genetics; D013256:Steroids / Q000627:therapeutic use
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids