Search for New Genetic Causes of Hypercalcemia by Massively Parallel Sequencing of a Genes Panel

NCT02908542 | Completed

• 1 other identifier: 16-048
• Study Type: observational
• Target: 185
• Locations: 1 country
• Sites: 1

Brief Summary

Hypercalcemia, whether chronic or acute, exposes the patient to potentially serious complications (arrhythmias, nephrolithiasis, nephrocalcinosis, ...). Prevention relies primarily on effective etiological necessary for taking matched load. Under the French reference center for rare disorders of calcium and phosphorus, the investigators looked for mutations in the coding sequence of the CYP24A1 gene (encoding the enzyme responsible for the breakdown of vitamin D), among patients with hypercalcemia without hyperparathyroidism with hypersensitivity to vitamin D. However, only 25% of these patients have a genetic anomaly suggesting the involvement of other genes (Molin et al. 2015). Recently our team, combined with Kaufmann et al. (2014 JCEM) validated the interest of the determination of metabolites of vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS / MS), as biological pre-screening stage for patients with hypercalcemia. The objective of this project is to complement the molecular and biochemical studies of patients without mutation of the coding sequence of CYP24A1, in a gene candidate approach using massively parallel sequencing (MPS) which allows to study a panel of gene potentially involved in disorder of metabolism of calcium and phosphorus. Highlighted variations will be tested in silico, and if possible in vitro. The investigators will also use LC-MS / MS to evaluate in vivo the effects of these variations on the metabolism of vitamin D, to develop a genotype / phenotype correlation. The work carried out within the Genetics Department Caen University Hospital in collaboration with physicians of the rare disease reference center of the metabolism of calcium and phosphorus should identify new genetic mechanisms underlying hypercalcemia. At the time of development of personalized medicine, it will adapt the therapy in patients at risk for metabolic complications and / or kidney following administration of vitamin D and finally to offer genetic counseling.

Conditions

Hypercalcemia

Outcome Measures

Primary Outcomes (1)

• number of identified genetic variations presumed pathogenic

  3 years

Interventions

genetic analysis with massively parallel sequencing GENETIC

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with medical history of hypercalcemia without hyperparathyroidism

You may qualify if:

• Chronic hypercalcemia or at least one episode of acute hypercalcemia not linked to hyperparathyroidism
• Another genetic disorder identified with hypercalcemia (eg Williams-Beuren syndrome)
• Primary hyperparathyroidism (high PTH)
• neoplasia
• granulomatosis

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

Caen Hospital University

Caen, 14033, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood or DNA samples

MeSH Terms

Conditions

Hypercalcemia

Interventions

Genetic Testing; High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Sequence Analysis

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2016
• First Posted: September 21, 2016
• Study Start: December 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: December 1, 2018
• Last Updated: August 2, 2021

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)