ISSN: 1305-385X
Hakkında: Özel sayılar şeklinde yayınlanır.
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Hereditary Cystic Diseases Of The Kidney And Autosomal Dominant Polycystic Kidney Disease From A Genetic Point Of View
Dr. Kıvanç ÇEFLEa
aİç Hastalıkları AD, Tıbbi Genetik BD, İstanbul Üniversitesi İstanbul Tıp Fakültesi, İSTANBUL
Renal cysts may accompany the clinical spectrum of many monogenic diseases. However, they are the main determinant of the clinical course of certain hereditary kidney disorders such as autosomal dominant polycystic kidney disease (ADPKD). Hepatic cysts, intracranial aneurysms, mitral valve prolapse and inguinal hernias are the other manifestations of ADPKD. Its penetrance is 90% in carriers who lived up to 70 years. Two genes, PKD1 and PKD2 are responsible from the majority of cases (85-90% and 10-15%, respectively). No clear genotype-phenotype relation has been established at present and there is extensive intrafamilial expression. PKD2-associated disease is milder with slower progression to end-stage renal failure and life expectancy. olycystin-1 and ?2 encoded by PKD1 and PKD2 function as a "mechanosensor" in the primary cilia of tubuler epithelium. The insensitivity of this mechanosensor due to PKD1 or PKD2 mutations may impair transepitheliail transport and lead to cyst formation. According to the "two-hit" hypothesis, other than the germline mutation (first hit), a somatic mutation (second hit) in the normal allele is necessary for cystogenesis. Molecular studies performed in cystic epithelial cells and transgenic animal experiments supplied substantial evidence supporting this view.Keywords: Autosomal dominant polycystic kidney disease, geneticsTurkiye Klinikleri J Int Med Sci 2005, 1(4):6-11
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