Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

Acquired cystic kidney disease following long-term peritoneal dialysis for congenital nephrotic syndrome.

We describe here the clinicopathological findings in a child with congenital nephrotic syndrome (CNS) non-responsive to medical therapy who developed acquired cystic kidney disease (ACKD) in both native kidneys after long-term peritoneal dialysis. This case indicates that CNS is a further pathologic condition related to the development of ACKD.

Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa.

We report the occurrence of congenital nephrotic-range proteinuria secondary to focal segmental glomerulosclerosis in an infant with epidermolysis bullosa and pyloric atresia. A homozygous missense mutation, R1281W, in exon 31 of the beta4 integrin gene, ITGB4, was identified. By immunofluorescence, beta4 integrin expression was reduced in both dermal keratinocytes and glomerular podocytes. This is the first demonstration of beta4 integrin expression in human glomeruli. We postulate a role for altered beta4 integrin function in the mediation of the glomerular permeability defect.

Diffuse mesangial sclerosis: a unique type of congenital and infantile nephrotic syndrome.

Clinical and pathological findings in four Turkish infants with isolated diffuse mesangial sclerosis (DMS) are presented. All the patients were offsprings of consanguineous marriages and two had similarly affected sibs indicating an autosomal recessive inheritance. The onset of the nephrotic syndrome was at 7, 17, 11 and 3 months of age. They all died in a state of renal failure complicated by infections at the ages of 11, 33, 13 and 5 months. DMS was diagnosed at postmortem examination in all. Fluorescence-microscopical studies in all and an electron-microscopical study in one revealed nonspecific findings. The shorter survival in three of the cases was thought to be due to intervening infections. The variation of the clinical features along with the fluorescence and electron-microscopical findings are consistent with the previously mentioned heterogeneous aspect of DMS.

Proteinosis lipoide (Hyalinosis cutis et mucosae) / Lipoid proteinosis (Hyalinosis cutis et mucosae)

Exponemos el primer caso de Proteinosis lipoid or hyd o Hyalinosis cutis et mucosae en el Perú, una rara genodermatosis benigna, en un niño de 7 años cuyos progenitores son hermanos de padre, presentando desde muy temprana edad ronquera, cicatrices varioliformes y exulceraciones castrosas, mostrando histológicamente depósitos de sustancia hialina en la porción papilar de la dermis y alrededor de los vasos sanguíneos adyacentes, además de revisar brevemente sus rasgos clínicos, patogénicos, histológicos y de evolución

A clinicopathologic study of forty-eight infants with nephrotic syndrome.

The clinical and histopathologic features of 48 children presenting with the nephrotic syndrome during the first year of life were analyzed. Proteinuria was discovered soon after birth to 3 months of age in 39 infants (congenital nephrotic syndrome), and nine infants had an infantile onset presenting between 4 and 12 months of age. Neither histologic parameters--microglomeruli, epithelial, or mesangial proliferation, focal segmental or global sclerosis, fibrinoid necrosis, or tubular microcysts--nor histologic classification--microcystic disease, mesangial proliferative glomerulonephritis, focal segmental glomerular sclerosis/hyalinosis-predicted the outcome. Rather, age at presentation was found to predict outcome: One of 39 infants with a congenital onset and seven of nine infants with an infantile onset underwent a complete remission (P less than 0.0001).

Congenital glomerulosclerosis and nephrotic syndrome in two infants. Speculations and pathogenesis.

The incidental finding of hyalinized glomeruli in otherwise normal infant kidneys is referred to as congenital glomerulosclerosis. Two infants had extensive glomerulosclerosis manifested by nephrotic syndrome, severe oliguria, and progressive renal failure. Both patients were believed to have had intrauterine infections. These two cases have unequivocally identified congenital glomerulosclerosis as one of the causes of nephrotic syndrome in infancy. In addition, they suggest that extensive glomerulosclerosis in some cases may be a result of congenital infections.