Clinical Investigation And Gene Screening In A Family With Hereditary Kidney Disease

Objective To identify the hereditary feature and clinical characteristics in a family withhereditary kidney disease.Probable diagnoses were analyzed and molecular hereditarymechanism was explored.Materials and Methods1. Pedigrees：The family consisted of three generations and twenty-eight members.Theproband’s grandfather and grandmother were the first generation.The second generationcomprised three sons,three daughters and their spouses.The third generation included twelvemembers.2. Laboratory and imaging examination：Blood routine,urinary routine and renal functionindicators were examined.Further investigation including urinary chemistry,urine red cellmorphology and kidney imaging were performed in suspected members.3. Kidney biopsy：Percutaneous renal biopsy was performed for the proband,the proband’syounger brother and one suspected member. Light microscopical,electron microscopical andimmunohistochemical examination were performed.4. Genetic screening：Gene sequencing was performed on exon4-5of UMOD, PLCE1, NPHS2,ACTN4and WT1.Results1. Clinical characteristics：Four male members in the family were diagnosed as hereditarykidney disease,two of whom died of uremia.The patients presented with chronic renalinsufficiency,with negative or mild proteinuria. Edema, hypertension and oliguria were absent.2. Renal biopsy findings：Sclerosing glomerulonephritis were observed in renal biopsyspecimens from the proband and focal segmental glomerular sclerosis were observed in renalbiopsy specimens from the proband’s younger brother. Both showed focal tubular atrophy anddilation,accompanied with interstitial inflammation.3. Gene sequencing（the proband and his younger brother）：1UMOD single nucleotide polymorphisms (SNP)(P.Gly88Gly) was found in the proband;5SNPs (2synonymous SNP,3non-synonymous SNP) were found in PLCE1: P.Cys270Cys、P.Glu320Glu、P.Thr1777Iie、P.His1927Arg were found in the proband,P.Arg1575Pro was found in the proband and theproband’s younger brother;2NPHS2SNPs (P.Gly34Gly,P.Ala318Ala) were found in theproband and the proband’s younger brother;2ACTN4SNPs (P.Pro179Pro，P.Leu855Leu) werefound in the proband and the proband’s younger brother;2WT1SNPs (P.Pro110Pro，P.Arg369Arg) were found in the proband and the proband’s younger brother.Conclusion1. Based on clinical characteristics、renal pathology and gene sequencing results,we speculatedmedullary cystic kidney disease2might be the probable diagnosis.2. Although renal pathologist suggested of focal segmental glomerular sclerosis,disecrepancy inclinical feature were presented and possibility of familial focal segmental glomerular sclerosisseem slim.3. Variations of ACTN4,which exist only in the proband and his younger brother,might beassociated with the hereditary kidney disease.