[Genetic basis for malformation-associated uropathy and renal dysplasia].
The wide association between urinary tract malformations and dysplastic kidneys, known as CAKUT (Congenital Anomalies of the Kidney and Urinary Tract), could be caused by a single disorder of the embryonic development of the kidney and urinary tract. These complex patterns of development are under genetic control. A positive family history strongly suggests a genetic origin of these conditions. Linkage studies show an extreme genetic heterogenicity and an important phenotypic and clinical variability of the same mutation. Some urinary tract malformations have been investigated in the context of clinical syndromes. The renal-coloboma syndrome is an autosomal dominant human disease, secondary to mutation of the PAX2 transcription factor, characterized by optic nerve coloboma, renal anomalies and vesicoureteral reflux. However, most of the urinary tract anomalies can occur in isolation. Studies have shown the association of hereditary hydronephrosis with HLA antigens on chromosome 6 and the association of VUR with the mutations in a locus of chromosome 1. The higher frequency and severity of some uropathies in the male gender may be explained by a linkage-disequilibrium phenomenon or a X-linked transmission pattern. For example, the mutations in the AGTR2 gene on chromosome X were observed in animal models but not yet confirmed in human subjects. Finally, the ACE gene polymorphism is associated with a higher incidence of congenital hypo-dysplastic kidneys and represents a significant risk factor for the development of progressive renal damage.
Dialisi e Nefrologia Pediatrica, Clinica De Marchi, Istituti Clinici di Perfezionamento, Milano, Italy.
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Barberis
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Edefonti
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Cusi
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Marra
D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003103:Coloboma / Q000235:genetics; D000013:Congenital Abnormalities / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000473:pathology*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D005810:Multigene Family; D009900:Optic Nerve / Q000002:abnormalities; D051762:PAX2 Transcription Factor; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011487:Protein Conformation; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014551:Urinary Tract / Q000002:abnormalities* / Q000196:embryology; D014718:Vesico-Ureteral Reflux / Q000235:genetics; D014960:X Chromosome
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C497319:Pax2 protein, mouse; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014157:Transcription Factors; D007703:Peptidyl-Dipeptidase A