title: 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.
authors.affiliation: Laboratory of Human Reproductive Genetics, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Bouba
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Siomou
authors.forename: Constantinos J
authors.initials: CJ
authors.lastname: Stefanidis
authors.forename: Anastasia
authors.initials: A
authors.lastname: Emmanouilidou
authors.forename: Anna
authors.initials: A
authors.lastname: Galidi
authors.forename: Elissavet
authors.initials: E
authors.lastname: Hatzi
authors.forename: Sofia
authors.initials: S
authors.lastname: Markoula
authors.forename: Andromachi
authors.initials: A
authors.lastname: Mitsioni
authors.forename: Antigoni
authors.initials: A
authors.lastname: Siamopoulou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiou
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D009154:Mutation
chemical_list: C484298:HOXA11 protein, human; C489493:HOXD11 protein, human; D018398:Homeodomain Proteins