Human renal hypodysplasia gene investigated
For adults with chronic renal failure (CRF), medication with angiotensin converting enzyme (ACE) inhibitors is renoprotective. However, its effectiveness is unproven in children with this disease. Lack of effective paediatric therapies provided the aim for project partners in ESCAPE_TRIAL to research the spectrum of factors involved in development and progression of CRF. One of the main causes of CRF in children is renal hypodysplasia, a syndrome characterised by low number of nephrons and abnormally small kidney size. Consequently, partners at the University Hospital for Pediatric and Adolescent Medicine in Heidelberg elected to research the genetics of this contributory factor. Previous animal and human pedigree studies had suggested a substantial genetic input for renal hypodysplasia and the team focused on one gene in particular, Uroplakin IIIA (UPIIIA). Coding for an important membrane protein of urothelial plaques, the UPIIIA gene has also been implicated as a potential source of kidney development problems in mouse models. Mutation analysis was performed on 170 paediatric patients suffering from severe renal hypodysplasia. Two heterozygous mutations were observed but for the first, a missense mutation, only one family showed results consistent with a disease-causing outcome. Segregation studies indicated that the second mutation was unlikely to cause CRF. The genetic data accumulated here suggests that mutations of UPIIIA in particular are infrequently a cause of renal hypodysplasia. However, research into genetic variation underlying renal development has other important implications. These include the discovery of polygenic traits for the disease and insights into the spectrum and mechanisms of genetic abnormalities.
