Konjenital ve Infantil Nefrotik Sendromlu Hastalarda Genotip-Fenotip İlişkisinin Değerlendirilmesi

Abstract

Nephrotic syndrome which is characterised with proteinuria, hypoalbuminemia, hyperlipidemia and edema is a lethal disease especially in the first year of life (congenital and infantile nephrotic syndrome). The mutations in genes coding structural and regulatory proteins of glomerular filtration barrier are the main causes of congenital and infantile nephrotic syndrome. This study aims to investigate the frequency of the genes responsible from nephrotic syndrome in the first year of life, the mutations in Turks and the relationship between genetic disorders and clinical findings in a large group of patients. We sequenced NPHS1, NPHS2, WT1 and LAMB2 genes in 102 congenital and infantile nephritic syndrome patients and we correlated the genetic findings with clinical data. We detected mutations in one of these 4 genes in 65% of the patients. 15 of these mutations were novel. Most of the mutations were detected in NPHS1 (%37). Mutation detection rate was two-folds higher in congenital nephrotic syndrome patients than infantile nephrotic syndrome patients (73% vs 36%). In congenital nephrotic syndrome patients most of the mutations were detected in NPHS1 (46%). In infantile nephrotic syndrome patients most of the mutations were in NPHS2 (%14) and WT1 (%14). Age at disease onset was significantly earlier in patients with NPHS1 mutations. Survival of the patients with NPHS2 mutations was significantly better than patients with mutations in other genes. Female patients with NPHS1 mutations had better survival rates compared to males with NPHS1 mutations. NPHS1 mutations affecting the extracellular domain of the protein were associated with worse survival rates compared with mutations affecting other domains of the protein. These results clearly demonstrate the genetic disorders causing congenital and infantile nephrotic syndrome in Turkey and association of genetic disorders with prognosis.