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Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis

Lookup NU author(s): Professor John SayerORCiD


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Background and objectives Nephrolithiasis is a prevalent condition that affects 10%-15% of adults in their lifetime. It is associated with high morbidity due to colicky pain, the necessity for surgical intervention, and sometimes progression to CKD. In recent years, multiple monogenic causes of nephrolithiasis and nephrocalcinosis have been identified. However, the prevalence of each monogenic gene in a pediatric renal stone cohort has not yet been extensively studied.Design, setting, participants, & measurements To determine the percentage of cases that can be explained molecularly by mutations in one of 30 known nephrolithiasis/nephrocalcinosis genes, we conducted a high-throughput exon sequencing analysis in an international cohort of 143 individuals <18 years of age, with nephrolithiasis (n=123) or isolated nephrocalcinosis (n=20). Over 7 months, all eligible individuals at three renal stone clinics in the United States and Europe were approached for study participation.Results We detected likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 16.8% (24 of 143) of affected individuals; 12 of the 27 detected mutations were not previously described as disease causing (44.4%). We observed that in our cohort all individuals with infantile manifestation of nephrolithiasis or nephrocalcinosis had causative mutations in recessive rather than dominant monogenic genes. In individuals who manifested later in life, causative mutations in dominant genes were more frequent.Conclusions We present the first exclusively pediatric cohort examined for monogenic causes of nephrolithiasis/nephrocalcinosis, and suggest that important therapeutic and preventative measures may result from mutational analysis in individuals with early manifestation of nephrolithiasis or nephrocalcinosis.

Publication metadata

Author(s): Braun DA, Lawson JA, Gee HY, Halbritter J, Shril S, Tan WZ, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Fisher B, Spaneas L, Varner J, Sayer JA, Milosevic D, Baum M, Tasic V, Hildebrandt F

Publication type: Article

Publication status: Published

Journal: Clinical Journal of the American Society of Nephrology

Year: 2016

Volume: 11

Issue: 4

Pages: 664-672

Print publication date: 07/04/2016

Online publication date: 19/01/2016

Acceptance date: 02/12/2015

ISSN (print): 1555-9041

ISSN (electronic): 1555-905X

Publisher: American Society of Nephrology


DOI: 10.2215/CJN.07540715


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Funder referenceFunder name
2015R1D1A1A01056685Basic Science Research Program through National Research Foundation of Korea by Ministry of Education
6-FY11-241March of Dimes Foundation
DK064614National Institutes of Health
DK1068306National Institutes of Health
DK1069274National Institutes of Health