Mutation analysis of genes in a family with proteinuria syndrome

Abstract

Objective To investigate the clinic features of a family present with proteinuria and microscopic hematuria, and screen 3 commonly pathogenic genes of hereditary proteinuria syndrome. Methods Clinical data of a family present with proteinuria and microscopic hematuria were collected and analyzed.Pedigree of the family was drawn.Urine screening was conducted to all members of the family.Peripheral blood was taken from all members of the family.Direct sequencing of all exons of NPHS1 and NPHS2 gene and exon 8, 9 of WT1 gene was performed on 2 patients and their parents. Results The family had 3 generations, 17 members.There were 2 sibling patients in the family.One was a female, the other was male.The average age onset was 1.3 years.Analysis of clinical data revealed the family genetic features was consistent with the autosomal recessive inheritance.The proband presented with initial steroid-resistant nephrotic syndrome.His renal pathological changes under light microscope showed focal proliferative glomerulonephritis.Under immunofluorescence microscope IgA, IgM, C1q and C3 were all negative, but type Ⅳ collagen α1, α3 and α5 chains were positive.The basement membrane was normal, and foot process fusion was found under the electron microscope.Two patients both had heterozygous p. R138Q(c.413G>A) and p. L156FfX11(c.467-468insT) in the NPHS2 gene exon 3 and 4.Analysis mutation of NPHS2 gene in the family revealed that p. R138Q missense mutation and p. L156FfX11 frameshift mutation were from their parents, respectively.Two mutations had been reported before, which were disease-causing mutation.The former was the most common mutation of NPHS2 gene in European population, but the latter only had been reported in the Chinese population. Conclusions The p. L156FfX11 mutation may be a specific mutation in Chinese children with nephrotic syndrome.Mutations of NPHS2 gene can not only cause proteinuria, but also be associated with microscopic hematuria.Renal pathological changes caused by NPHS2 gene mutation could not only become focal segmental glomerulosclerosis, but also be focal proliferative glomerulonephritis.Renal pathological changes may simply reflect the course of the disease. Key words: Proteinuria syndrome; Proteinuria; NPHS2 gene; Hematuria; Child