ROBO2 gene variants are associated with familial vesicoureteral reflux
| Autor: | Carolina Grassia, Aida M. Bertoli-Avella, Silverio Perrotta, Francesca Punzo, Bianca M. de Graaf, Pier Francesco Rambaldi, Bruno Nobili, Maria Luisa Conte, Giuliana Lama, Ben A. Oostra, Angela La Manna, Cesare Polito |
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| Přispěvatelé: | BERTOLI AVELLA, A., Conte, M., Punzo, F., DE GRAAF, B., Lama, G., LA MANNA, A., Polito, C., Grassia, C., Nobili, Bruno, Rambaldi, Pier Francesco, Oostra, B., Perrotta, Silverio, Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent Urinary system Biology medicine.disease_cause urologic and male genital diseases Vesicoureteral reflux Exon Ureter Clinical Research medicine Missense mutation Humans Receptors Immunologic Child Genetics Vesico-Ureteral Reflux Mutation Genitourinary system Infant General Medicine medicine.disease female genital diseases and pregnancy complications Pedigree medicine.anatomical_structure Nephrology Ureteric bud Child Preschool ROBO2 vesicoureteral reflux Female |
| Zdroj: | Journal of the American Society of Nephrology, 19(4), 825-831. American Society of Nephrology |
| ISSN: | 1046-6673 |
| Popis: | The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted. |
| Databáze: | OpenAIRE |
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