Is CYP24A1 Heterozygosity a Risk Factor for Nephrolithiasis?

Обзор

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

Вмешательства

• Биопрепарат Supplementary blood samples for PBMC analysis at V2
  Supplementary blood (serum and plasma) and urines samples for bio collection at V3

Первичные конечные точки

• Prevalence of nephrolithiasis in patients who are CYP24A1 heterozygous and homozygous (or compound heterozygous) [Срок оценки: Visit 2 (at least 24 hours after baseline)]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 2 центра

• Hôpital Femme Mère Enfant — Bron
• Hôpital Edouard Herriot — Lyon

Идентификаторы

NCT: NCT07201701 · 69HCL25_0507 · 2025-A01749-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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