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Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis
- Publication Year :
- 2016
-
Abstract
- 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 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.
- Subjects :
- 0301 basic medicine
Male
Pediatrics
medicine.medical_specialty
Adolescent
Epidemiology
Urology
030232 urology & nephrology
Disease
Critical Care and Intensive Care Medicine
Nephrolithiasis
Kidney Calculi
03 medical and health sciences
High morbidity
0302 clinical medicine
medicine
Prevalence
Humans
Hypercalciuria
Child
Exome sequencing
Transplantation
business.industry
Infant
Original Articles
medicine.disease
Mutational analysis
Nephrocalcinosis
030104 developmental biology
Europe
child
exons
genes, dominant
genetic renal disease
humans
hypercalciuria
kidney stones
mutation
nephrocalcinosi
Nephrology
Child, Preschool
Cohort
Mutation
Kidney stones
Female
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2b7eca2ebcfbb46312592566570fa95c