Renal complications in 6p duplication syndrome: Microarray‐based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS)

Abstract

6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end-stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4-Mb duplication at 6p25.3-p25.1 with 32 protein-coding genes and a 220-Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non-coincidental complication. FOXC1, located within the 6.4-Mb duplicated region at 6p25.3-p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT.

Glomerulopathy in patients with distal duplication of chromosome 6p

“…1d ). A review of the published cases along with database search [ 1 – 7 ] allowed for identification of 12 individuals whose region of duplication was partially overlapping with the region affected in our case (Fig. 1c ).…”

“…Renal abnormalities have been observed in approximately half of the patients. Congenital abnormalities of the kidney and urinary tract (CAKUT), such as hypoplastic kidneys, renal cysts, vesicoureteral reflux and hydronephrosis have been described [ 4 , 6 , 7 ]. In addition, proteinuria has been reported in eight patients.…”

“…In addition, proteinuria has been reported in eight patients. These included two cases of a pure 6p duplication [ 5 , 7 ] and six with a duplication resulting from an unbalanced parental translocation (after [ 4 , 7 – 9 ]). The presented case is, however, the first to be comprehensively studied for mutations in all known glomerulopathy-associated genes to rule out co-incidence of two genetic entities.…”

How to diagnose and follow patients with glomerulonephritis without kidney biopsy?

“…Other genomic studies re veal multiple risk loci involved in, for example, renal function decline in individuals of European descent, the development of chronic kidney dis ease (CKD), congenital anomalies of the kidney and urinary tract, focal segmental glomerulone phritis, and others. 3,7 Clearly, one of the main obstacles of GWAS is the number of the diseased patients and prop erly matched healthy control individuals that It is clear that kidney function differs between the diseases, but also depends on such factors as sex or age. Thus, if one measures factor X in glo merulonephritis A, one should precisely know how it behaves in glomerulonephritis B, C, D, or others, or how it behaves in men or women at different ages with or without concomitant diseases, such as diabetes, hypertension, vascu litis, or cancer.…”

“…On the one hand, this effec tively limits the numbers of single nephrology centers to think about, but on the other hand, it promotes an international cooperation, which in the last years have yielded numerous break through results. [3][4][5]7 The next group consists of the transcriptomic based studies that concentrate on the gene or genes either defined earlier by GWAS or simply proposed by authors as potential biomarkers that are believed to be involved in the disease. There are also many research projects focused on the role of microRNAs (miRNAs), a small noncoding RNA molecules that regulate gene expression.…”