Clinical trial NCT02908542: Search for New Genetic Causes of Hypercalcemia by Massively Parallel Sequencing of a Genes Panel
Official title: Search for New Genetic Causes of Hypercalcemia by Massively Parallel Sequencing of a Genes Panel
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypercalcemia
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2016-09-21
Enrollment: 185
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with medical history of hypercalcemia without hyperparathyroidism

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.


Eligibility criteria: Inclusion criteria

* Chronic hypercalcemia or at least one episode of acute hypercalcemia not linked to hyperparathyroidism
* Consent to the realization of a genetic analysis for medical purposes Non-inclusion criteria
* Another genetic disorder identified with hypercalcemia (eg Williams-Beuren syndrome)
* Primary hyperparathyroidism (high PTH)
* neoplasia
* granulomatosis

Primary outcomes:
measure: number of identified genetic variations presumed pathogenic
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Caen
country: France
facility: Caen Hospital University
Study officials:
References: