The Turkish Journal of Pediatrics 2014 , Vol 56 , Num 4
Diverse Phenotypic Expression of NPHP4 Mutations in Four Siblings
1Division of Pediatric Nephrology, Department of Pediatrics and 2Department of Pathology, Gazi University, Faculty of Medicine, Ankara, Turkey, and 3Department of Pediatrics and Human Genetics, University of Michigan, Michigan, USA
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. Keywords : hereditary nephropathy, nephronophtisis, NPHP4
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