Molecular characterization of a recurrent 10.9 kb CYP24A1 deletion in Idiopathic Infantile Hypercalcemia

Autor: Nadia Coudray, Genevieve Abeguile, Mireille Castanet, Marie-Laure Kottler, Philippe Eckart, Arnaud Molin, Hervé Mittre, Nicolas Richard, Marie Nowoczyn, Celine Ballandone
Přispěvatelé: Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Service de biochimie [CHU Caen], Œstrogènes, reproduction, cancer (OeReCa), Service de Pédiatrie Médicale [Caen], Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN)
Rok vydání: 2019
Předmět:
Male
Adolescent
DNA Copy Number Variations
Genetic counseling
030232 urology & nephrology
[SDV.GEN] Life Sciences [q-bio]/Genetics
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Bioinformatics
Genetic analysis
Infant
Newborn
Diseases
03 medical and health sciences
0302 clinical medicine
CYP24A1
Loss of Function Mutation
Genetics
medicine
Vitamin D and neurology
Humans
Hypercalciuria
Renal Insufficiency
Copy-number variation
Pathology
Molecular
Vitamin D
Child
Vitamin D3 24-Hydroxylase
Genetics (clinical)
Sequence Deletion
030304 developmental biology
[SDV.GEN]Life Sciences [q-bio]/Genetics
0303 health sciences
Massive parallel sequencing
business.industry
Infant
General Medicine
medicine.disease
3. Good health
Nephrocalcinosis
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Child
Preschool
Hypercalcemia
Female
business
Metabolism
Inborn Errors
Zdroj: European Journal of Medical Genetics
European Journal of Medical Genetics, Elsevier, 2018, 62 (11), pp.103577. ⟨10.1016/j.ejmg.2018.11.011⟩
ISSN: 1769-7212
Popis: International audience; Loss-of-function mutations in CYP24A1 (MIM 126065 20q13.2), the gene encoding the 24-hydroxylase responsible for 25-OH-D and 1,25-(OH)2D degradation, are identified in about 20% of patients presenting Idiopathic Infantile Hypercalcemia (IIH) (MIM 143880). Common features of this autosomal recessive condition included hypercalcemia with hypercalciuria, suppressed PTH and a high 25-OH-D3:24,25-(OH)2D3 ratio. Medical care mainly relies on sun protection and life-long contraindication of vitamin D to avoid complications such as early nephrocalcinosis and renal failure.Molecular diagnosis therefore keeps a crucial place in the diagnosis of IIH, and genetic counseling should be systematically recommended to prevent vitamin D administration in affected siblings.In this report is described the molecular characterization of a CYP24A1 deletion identified in two unrelated families. This highlights the potential role of CYP24A1 copy number variations (CNV) in IIH. Considering the presence of CNV affecting CYP24A1 in public databases, CNV analysis should be systematically added to the sequencing studies in IIH. Targeted Massively Parallel Sequencing (MPS) study coupled with a CNV detection tool called CovCop is a powerful method to detect genic rearrangement and improve genetic analysis.
Databáze: OpenAIRE
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