title: Diverse phenotypic expression of NPHP4 mutations in four siblings.
abstract: Nephronophthisis (NPHP) is an autosomal recessive disease characterized by renal tubular basement membrane disruption, interstitial fibrosis and tubular cysts that progresses to end-stage kidney disease (ESKD). There are also characteristic extrarenal manifestations. Mutations of more than thirteen genes that can cause NPHP have been identified. We herein report four siblings from a consanguineous family, who carried the same NPHP4 mutations but presented with different disease phenotypes ranging from enuresis nocturna to ESKD. Diluted urine and echogenic kidneys in ultrasound examination were consistent, which is typical for 100% of the NPHP cases that have been described. Chronic kidney disease developed in the older two brothers. The observed phenotypic differences are likely to be related to environmental and epigenetic factors, oligogenic inheritance and modifier genes affecting the age of presentation of signs and symptoms. NPHP should be considered as an important cause of CKD in children, which insidiously progresses to ESKD, with no specific therapy available.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Gazi University, Faculty of Medicine, Ankara, Turkey. sevcan@gazi.edu.tr.
authors.forename: Sevcan A
authors.initials: SA
authors.lastname: Bakkaloğlu
authors.forename: Yaşar
authors.initials: Y
authors.lastname: Kandur
authors.forename: Tuğba
authors.initials: T
authors.lastname: Bedir-Demirdağ
authors.forename: İpek
authors.initials: İ
authors.lastname: Işık-Gönül
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D035781:Siblings; D055815:Young Adult
chemical_list: C491578:NPHP4 protein, human; D011506:Proteins; D004247:DNA
references.citation: Nat Genet. 1997 Oct;17(2):149-53
references.pmid: 9326933
references.citation: Am J Kidney Dis. 2004 Feb;43(2):358-64
references.pmid: 14750102
references.citation: Pediatr Nephrol. 2009 Dec;24(12):2333-44
references.pmid: 18607645
references.citation: Nat Genet. 2002 Oct;32(2):300-5
references.pmid: 12244321
references.citation: J Am Soc Nephrol. 2007 Jun;18(6):1855-71
references.pmid: 17513324
references.citation: Curr Opin Genet Dev. 2005 Jun;15(3):324-31
references.pmid: 15917209
references.citation: Hum Mutat. 2005 Apr;25(4):411
references.pmid: 15776426
references.citation: Am J Hum Genet. 2002 Nov;71(5):1161-7
references.pmid: 12205563
references.citation: J Am Soc Nephrol. 2011 Nov;22(11):2047-56
references.pmid: 22034641
references.citation: J Nephrol. 1998 Sep-Oct;11(5):224-8
references.pmid: 9831234
references.citation: Kidney Int. 1997 Jan;51(1):261-9
references.pmid: 8995741
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98 (17 ):9784-9
references.pmid: 11493697
references.citation: J Am Soc Nephrol. 2007 Oct;18(10):2789-95
references.pmid: 17855640
references.citation: Nephrol Dial Transplant. 2006 Sep;21(9):2660-3
references.pmid: 16782989
references.citation: Hum Genet. 2013 Aug;132(8):865-84
references.pmid: 23559409
references.citation: Am J Hum Genet. 2002 May;70(5):1240-6
references.pmid: 11920287
references.citation: Hum Mol Genet. 2009 Dec 15;18(24):4711-23
references.pmid: 19755384