NPHS2 mutations account for only 15 % of nephrotic syndrome cases

BMC Medical Genetics

Research Article

Marcela L. Souza¹  Maricilda P. De Mello¹  Suéllen R. de Souza¹  Mara Sanches Guaragna¹  Taciane B. Henriques¹  Cristiane SC Piveta²  Gil Guerra-Junior³  Andréa T. Maciel-Guerra⁴  Anna Cristina GB Lutaif⁵  Vera MS Belangero⁵ 

[1] Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, Caixa Postal 6010, São Paulo, Brasil;Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, Caixa Postal 6010, São Paulo, Brasil;Centro de Investigação em Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Centro de Investigação em Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Grupo Interdisciplinar de Estudos da Determinação e Diferenciação do Sexo, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Endocrinologia Pediátrica, Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Departamento de Genética Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Grupo Interdisciplinar de Estudos da Determinação e Diferenciação do Sexo, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;Nefrologia Pediátrica, Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil;

关键词: Steroid-resistant nephrotic syndrome;    Children;    Adolescents;    Mutations;    NPHS2;    NPHS1;    WT1;   

DOI  :  10.1186/s12881-015-0231-9

 received in 2015-02-11, accepted in 2015-09-15,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundNephrotic syndrome is traditionally classified on the basis of the response to standard steroid treatment. Mutations in more than 24 genes have been associated with nephrotic syndrome in children, although the great majority of steroid-resistant cases have been attributed to mutations in three main genes: NPHS1, NPHS2 and WT1. The aims of this study were to identify mutations in these genes more frequently reported as mutated and to characterize each variation using different in silico prediction algorithms in order to understand their biological functions.MethodsWe performed direct sequence analysis of exons 8 and 9 of WT1, 8 exons of NPHS2 and 29 exons of NPHS1, including NPHS2 and NPHS1 intron–exon boundary sequences, as well as 700 bp of the 5′ UTR from both genes in 27 steroid-resistant patients aged between 3 months and 18 years.ResultsAnalysis of the NPHS2 gene revealed four missense mutations, one frameshift mutation and three variations in the 5′ UTR. Four patients presented compound heterozygosis, and four other patients presented one heterozygous alteration only. WT1 and NPHS1 gene analysis did not reveal any mutations.DiscussionThis is the first study focusing on genetics of SRNS in Brazilian children. Identification of mutations is important because it could influence physicians’ decision on patient treatment, as patients carrying mutations can be spared the side effects of immunosuppressive therapy and ultimately could be considered for kidney transplantation from a living donor.ConclusionsAfter molecular analysis of the genes more frequently reported as mutated in 27 steroid-resistant nephrotic syndrome patients, we identified NPHS2 mutations confirming the hereditary character of the kidney disease in only 14.8 % of patients. Therefore, the next step is to perform a next generation sequencing based analysis of glomeluropathy-related panel of genes for the remaining patients in order to search for mutations in other genes related to steroid-resistant nephrotic syndrome.

【 授权许可】

CC BY   
© Guaragna et al. 2015