ABSTRACT
Renal cysts are common malformation during the prenatal and postnatal period and frequent cause of chronic kidney or ESRD. More than 70 genes have been shown to play role in their pathology. Part of them are responsible for the structure and function of the cilia, which assigns a large proportion of the renal cystic diseases in the ciliopathies. Another group of genes responsible for cystic kidneys encodes transcription factors with crucial role during organogenesis. We describe here a systematic approach for identifying the genetic cause(s) of an unusually severe form of renal cystic disease in a family with multiple affected siblings. High throughput mutations screening of the parents and one of the children was applied for identifying the genetic causes of the disease. The affected child was found to have inherited 3 deleterious mutations in two nephronophthisis genes, NPHP3 and NPHP4. The possibility for epistatic interaction of the NPHP mutations as well as the modifying effect of other inherited genetic variants is discussed.
