NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described

作者：Guaragna Mara S^*; Cleto Thais Lira; Souza Marcela Lopes; Lutaif Anna Cristina G B; Goncalves de Castro Luiz Claudio; Moreira Guimaraes Penido Maria Goretti; Maciel Guerra Andrea T; Belangero Vera M S; Guerra Junior Gil; De Mello Maricilda P

来源：Nephrology, 2016, 21(9): 753-757.

DOI：10.1111/nep.12667

• congenital nephrotic syndrome
• nephrin
• novel mutation
• NPHS1 gene

AimAutosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3months of life. NPHS1 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 NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease.
MethodsDirect sequencing of NPHS1 gene in four children was performed.
ResultsEach 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-frame 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
ConclusionsDespite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 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.
Summary at a Glance In this manuscript, the authors reported mutations in the nephrin gene (NPHS1) in 4 cases of congenital nephrotic syndrome from South Eastern region of Brazil. Although the number of patients described in this manuscript is small, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation.

• 出版日期2016-9