title: A familial case of severe infantile nephronophthisis explained by oligogenic inheritance.
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.
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Valentin
authors.initials: V
authors.lastname: Penchev
authors.affiliation: SBAL Pediatric Diseases, Nephrology and Hemodialysis Clinic, Department of Pediatrics, Medical University of Sofia, Sofia 1606, Bulgaria.
authors.forename: Anelia
authors.initials: A
authors.lastname: Boueva
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Kunka
authors.initials: K
authors.lastname: Kamenarova
authors.affiliation: SBAL Pediatric Diseases, Nephrology and Hemodialysis Clinic, Department of Pediatrics, Medical University of Sofia, Sofia 1606, Bulgaria.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Roussinov
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Reni
authors.initials: R
authors.lastname: Tzveova
authors.affiliation: National Genetic Laboratory, University Obstetrics and Gynecology Hospital "Maichin Dom", Sofia 1463, Bulgaria; Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", Sofia 1164, Bulgaria.
authors.forename: Mariya
authors.initials: M
authors.lastname: Ivanova
authors.affiliation: University Obstetrics and Gynecology Hospital "Maichin Dom", Department of Obstetrics and Gynecology, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Violeta
authors.initials: V
authors.lastname: Dimitrova
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Ivo
authors.initials: I
authors.lastname: Kremensky
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria.
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.affiliation: Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1463, Bulgaria. Electronic address: beltcheva@mmcbg.org.
authors.forename: Olga
authors.initials: O
authors.lastname: Beltcheva
mesh_terms: D000328:Adult; D002648:Child; D004843:Epistasis, Genetic; D005260:Female; D060045:Genes, Modifier; D006801:Humans; D007231:Infant, Newborn; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000235:genetics*; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*
chemical_list: C491578:NPHP4 protein, human; D011506:Proteins; C528697:nephrocystin-3, human; D016547:Kinesins
keywords: Ciliopathy; NGS; Nephronophthisis; Renal cysts