Is CYP24A1 Heterozygosity a Risk Factor for Nephrolithiasis? (HETEROCYP)

Civil Hospices of Lyon

Status

Not yet enrolling

Conditions

Nephrolithiasis

Treatments

Biological: Supplementary blood samples for PBMC analysis at V2

Study type

Observational

Funder types

Other

Identifiers

NCT07201701

69HCL25_0507

2025-A01749-40 (Other Identifier)

Details and patient eligibility

About

Biallelic loss-of-function variants in CYP24A1 have been identified as a common genetic cause of autosomal recessive hypercalcemia (ARH, ORPHA 300547, 1 in 80,000 live births), characterized by low PTH (parathyroid hormone) levels, a high 25-OH D/24,25-(OH)₂D ratio, and susceptibility to vitamin D intoxication.

In humans, heterozygous pathogenic variants in CYP24A1 have been proposed both as responsible for an autosomal dominant disorder and as a risk factor for nephrolithiasis, but the rarity and heterogeneity of human data prevent a definitive answer to this crucial question.

Nephrolithiasis is a complex disease in which nutritional factors - particularly sodium and protein intake (leading to hypercalciuria) - play a key role. It also has a heritability of 50%, suggesting the involvement of many genetic susceptibility factors, as well as monogenic forms (mainly autosomal recessive, but also dominant or X-linked), which have been identified in 10-20% of patients.

The increasing prevalence of nephrolithiasis, affecting approximately 10% of the general population over a lifetime, has a significant financial impact on healthcare systems and imposes a major burden of morbidity, justifying further investigation into the genetic underpinnings of nephrolithiasis.

The goal of the HeteroCYP project is to improve understanding of the phenotypes associated with heterozygous, compound heterozygous, and homozygous variants of CYP24A1 by comparing clinical and biological outcomes in patients according to their mutation type

Enrollment

45 estimated patients

Sex

All

Ages

2 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Group 1: Heterozygous Patients

Aged between 2 and 90 years
Weight > 12 kg
Carriers of a heterozygous CYP24A1 mutation
With or without symptoms: history of nephrocalcinosis or kidney stones

Group 2: Homozygous / Compound Heterozygous Patients

Aged between 2 and 90 years
Weight > 12 kg
Carriers of a homozygous or compound heterozygous CYP24A1 mutation
With or without symptoms: history of nephrocalcinosis or kidney stones

Exclusion criteria

Individuals unable to collect 24-hour urine
Individuals unable to be available for a full day in a day hospital (HDJ)
Pregnant, postpartum, or breastfeeding women
Individuals deprived of liberty by judicial or administrative decision
Individuals receiving psychiatric care
Individuals admitted to a healthcare or social institution for reasons other than participation in research
Adults under legal protection (guardianship or trusteeship)
Individuals not affiliated with a social security system or not benefiting from an equivalent scheme