{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:12:30Z","timestamp":1762866750956},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["FAPESP \u2010 2012\/51109\u20100 to MPdeM"],"award-info":[{"award-number":["FAPESP \u2010 2012\/51109\u20100 to MPdeM"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Autosomal recessive mutations in <jats:italic>NPHS1<\/jats:italic> gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests <jats:italic>in utero<\/jats:italic> or in the neonatal period during the first 3\u2009months of life. <jats:italic>NPHS1<\/jats:italic> encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the <jats:italic>NPHS1<\/jats:italic> gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the <jats:italic>NPHS1<\/jats:italic> gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Direct sequencing of <jats:italic>NPHS1<\/jats:italic> gene in four children was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in\u2010frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the <jats:italic>NPHS1<\/jats:italic> gene by describing a new mutation. Also, since we identified <jats:italic>NPHS1<\/jats:italic> pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.12667","type":"journal-article","created":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T17:58:56Z","timestamp":1447264736000},"page":"753-757","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<i>NPHS1<\/i> gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described"],"prefix":"10.1111","volume":"21","author":[{"given":"Mara S.","family":"Guaragna","sequence":"first","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering University of Campinas  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tha\u00eds Lira","family":"Cleto","sequence":"additional","affiliation":[{"name":"Nephrology Center of University Hospital Pedro Ernesto  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela Lopes","family":"Souza","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering University of Campinas  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Cristina G.B.","family":"Lutaif","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences University of Campinas  Campinas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Cl\u00e1udio Gon\u00e7alves","family":"de Castro","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Faculty of Medicine University of Brasilia  Brasilia, Federal District Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Goretti Moreira Guimar\u00e3es","family":"Penido","sequence":"additional","affiliation":[{"name":"Pediatric Department, Faculty of Medicine Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9a T.","family":"Maciel\u2010Guerra","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medical Sciences University of Campinas  Campinas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera M.S.","family":"Belangero","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences University of Campinas  Campinas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gil","family":"Guerra\u2010Junior","sequence":"additional","affiliation":[{"name":"Interdisciplinary study group of determination and sex differentiation, School of Medical Sciences University of Campinas, Campinas  Sao Paulo Brazil"},{"name":"Pediatric Research Center, School of Medical Sciences University of Campinas  Campinas Sao Paulo Brazil"},{"name":"Pediatric Endocrinology, Pediatric Department, School of Medical Sciences University of Campinas  Campinas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maricilda P.","family":"De Mello","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering University of Campinas  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,22]]},"reference":[{"issue":"27","key":"e_1_2_7_2_1","first-page":"1","article-title":"Heredity in the congenital nephrotic syndrome. 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