Congenital nephrotic syndrome with a novel NPHS1 mutation

Abstract

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessive disorder. The incidence of CNF is relatively high in Finland but considerably lower in other countries. We encountered a male newborn with CNF, associated with compound heterozygous mutations in nephrosis 1, congenital, Finnish type (NPHS1). The patient was admitted to hospital as a preterm infant. Physical and laboratory findings fulfilled the diagnostic criteria of nephrotic syndrome, and were compatible with a diagnosis of CNF, but there was no family history of the disease. On genetic analysis of NPHS1 a paternally derived heterozygous frame-shift mutation caused by an 8 bp deletion, resulting in a stop codon in exon 16 (c.2156-2163 delTGCACTGC causing p.L719DfsX4), and a novel, maternally derived nonsense mutation in exon 15 (c.1978G>T causing p.E660X) were identified. Early genetic diagnosis of CNF is important for proper clinical management and appropriate genetic counseling.

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

“…5,[8][9][10] Many genetic analyses have also revealed the importance of these gene mutations in the development of nephrotic syndrome in humans. [11][12][13][14][15][16][17][18][19][20] Thus, we were compelled to elucidate how these backbone proteins are physiologically localized and preserved in podocytes. Actually, scaffold proteins such as podocin, CD2-associated protein (CD2AP), and Zonula occludens-1 (ZO-1) are reported to be involved in stabilizing these backbone proteins.…”

Epigenetics in diabetic nephropathy, immunity and metabolism

“…These highly specialised cells derive their name from long interdigitating foot processes that form intercellular clefts called slit pores, bridged by diaphragms consisting of podocyte-specific proteins, such as NPHS1 (also known as nephrin) and NPHS2 (also known as podocin). Structural disturbance of the slit diaphragm proteins results in insufficient filtration and proteinuria, exemplified by congenital kidney failure arising from defects in nephrin [ 33 ]. Podocyte injury and loss, through detachment, apoptosis, or epithelial to mesenchymal transition (EMT) [ 34 ], are strong predictors of diabetic nephropathy progression [ 35 ] and are closely linked to glomerulosclerosis [ 36 ].…”

Congenital Nephrotic Syndrome With a Novel Presentation in Saudi Arabia

“…One of the main types of this syndrome is called the Finnish type, an autosomal recessive disorder. Finnish-type CNS usually results from a monogenic mutation in the NPHS1, which form the glomerular filtration barrier [1][2][3]. This gene is the most common gene among the Saudi population that causes CNS according to multiple studies performed in different regions of the kingdom [4].…”

“…This gene is the most common gene among the Saudi population that causes CNS according to multiple studies performed in different regions of the kingdom [4]. Disruption of normal glomerular filtration results in urinary protein loss, leading to the development of the syndrome's triad [1][2][3]. Losing proteins such as gamma globulin and anticoagulants cause a decrease in immunity and thrombosis, respectively.…”