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 |
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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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