Anti-Laminin (full length) polyclonal antibody [Biotin]

Steroid-resistant nephrotic syndrome (SRNS) represents a frequent cause of end-stage renal disease in children. Renal histology shows focal segmental glomerulosclerosis in about 80% of cases. Recently, it became apparent that up to 28% of all cases of childhood nephrotic syndrome are caused by recessive mutations of podocin (NPHS2). Additional monogenic causes are mutations of nephrin (NPHS1), WT1, PLCE1, or LAMB2. The related gene products are expressed in the glomerular podocyte and are essential for development and maintenance of the glomerular filtration barrier. These genetic insights have led to a better understanding of the pathogenesis of SRNS and will allow for unequivocal molecular genetic diagnostics and for stratification in therapeutic studies.

Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct eye abnormalities with microcoria reported as the most prominent clinical feature. LAMB2 mutations leading to lack of laminin beta 2 were identified as the molecular cause underlying Pierson syndrome. Although LAMB2 is known to be expressed in the neuromuscular system, and defects of the neuromuscular junctions had been found in laminin beta 2-deficient mice, no consistent neurological phenotype has been described clinically in murine or human laminin beta 2-deficiency before. This is likely clue to the early lethality from renal failure. Here we provide a detailed description of neurological manifestations and development in four patients affected by Pierson syndrome, who survived until the age of 1.3-4.8 years owing to renal replacement therapy. Severe muscular hypotonia, psychomotor retardation, and blindness were present in three patients harboring truncating mutations on both LAMB2 alleles. These symptoms were not attributable to complications of chronic renal failure, thus representing a primary feature of the genetic disorder. Alterations in skeletal muscle tissue from one case were compatible with a chronic denervating process. one affected girl, however, exhibited a milder course of renal disease, normal development, and preserved vision, presumably owing to some residual LAMB2 function. Our findings indicate that severe neurodevelopmental deficits have to be considered as part of Pierson syndrome, at least in the presence of biallelic functional null mutations (complete lack of laminin beta 2). This is an important issue in the counseling of parents of an affected newborn or infant. (c) 2007 Wiley-Liss, Inc.