title: NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome.
abstract: Recent discoveries indicate that the molecules in glomerular podocytes and slit diaphragms may play an important role in the development of proteinuria and nephrotic syndrome. Mutational analyses of NPHS1 and NPHS2 were performed to verify this hypothesis in sporadic nephrotic syndrome (NS) patients. Clinical characteristics and DNA samples were collected from 38 Chinese children with sporadic steroid-sensitive NS, 22 with steroid-resistant NS and 30 controls. Direct sequencing was performed after PCR amplification of all 29 and 8 exons of the NPHS1 and NPHS2 genes, respectively. In NPHS1, 4 patients had heterozygous missense mutations leading to amino acid substitutions (R800C, Q453R). Furthermore, 3 known single nucleotide polymorphism (SNP) were found (T741T, V763V, S1105S). In NPHS2, 3 patients had novel heterozygous allelic variants leading to amino acid substitutions (S206I, E188D), while 1 patient was found to carry a novel nonsense mutation leading to a truncated protein product (Glu237STOP). Two known polymorphisms were also found (A318A, L346L). The results demonstrate that NPHS1 and NPHS2 mutations are also present in Chinese sporadic NS patients, suggesting that genetic changes of nephrin and podocin may play pathogenetic roles in some patients with sporadic steroid resistant NS.
authors.affiliation: Department of Nephrology, Zhejiang University School of Medicine, Children's Hospital, Hangzhou 310006, Zhejiang Province, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Mao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lizhong
authors.initials: L
authors.lastname: Du
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Dai
authors.forename: Weizhong
authors.initials: W
authors.lastname: Gu
authors.forename: Ai'min
authors.initials: A
authors.lastname: Liu
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Shang
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D001483:Base Sequence; D002648:Child; D002681:China; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin