Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations

Abstract

Experimental studies have shown that homeobox genes are essential for the development of the kidney and urinary tract. Hoxa11/Hoxd11 double mutant mice demonstrate renal agenesis or hypoplasia. Since, to our knowledge, these genes have never been examined for alterations in humans with congenital anomalies of the kidney and urinary tract (CAKUT), we investigated whether mutations of HOXA11/HOXD11 genes are associated with non-syndromal congenital renal parenchymal malformations. DNA samples from 26 unrelated children with unilateral renal agenesis (URA), 20 with renal hypodysplasia (RHD) and 13 with multicystic dysplastic kidney (MCDK) were included in the study. Exons 1 and 2 of the HOXA11/HOXD11 genes were amplified individually by polymerase chain reaction (PCR) using 12 unique oligonucleotide primers. Single-strand conformation polymorphism (SSCP) analysis of overlapping polymerase chain reaction products was performed. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of the 59 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the hypothesis that mutations in the HOXA11/HOXD11 coding regions are involved in the pathogenesis of human non-syndromal congenital renal parenchymal malformations. Further studies are necessary, since other genes known to affect nephrogenesis, as well as genetic and environmental factors, may be involved.

Mutation screening of BMP4 and Id2 genes in Chinese patients with congenital ureteropelvic junction obstruction

“…Both genetic and environmental factors may play roles in the renal and urinary tract malformations. Although a few studies had been taken to screen mutations of the candidate genes and several mutations were found in patients with congenital anomaly of kidney and urinary tract (CAKUT) [4,5,14,17,28,29,31,40]. To our knowledge, this is the first study to detect mutations of BMP4 and Id2 genes in patients with congenital UPJO.…”

Genetics of congenital anomalies of the kidney and urinary tract

“…For example, despite severe renal phenotype observed in ROBO2/SLIT2-mutant mice, which includes formation of supernumerary ureters [44], these gene mutations are very rarely associated with familial nonsyndromic VUR in children [71,72]. Similarly, mutations in homeobox A11 and D11(HoxA11/HoxD11), which cause renal hypoplasia in mice [73], are not associated with CAKUT in children [74]. In addition, uroplakin (UP) UPII or UPIIIA mutations, which, respectively, cause hydronephrosis or VUR in mice [75], are not detected in the majority of children with nonsyndromic cases of CAKUT.…”

A homozygous HOXA11 variation as a potential novel cause of autosomal recessive congenital anomalies of the kidney and urinary tract

“…So far, three independent studies comprising a total of 552 patients with CAKUT have searched pathogenic variants of HOX11 paralogs including HOXA11 , and none found any pathogenic variant associated with the autosomal recessive CAKUT phenotype 5,17,18 . This report, therefore, introduces the first relationship between a homozygous variation of HOXA11 and autosomal recessive CAKUT in humans.…”