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

Authors
  • Molin, Arnaud1
  • Nowoczyn, Marie2
  • Coudray, Nadia3
  • Ballandone, Céline4
  • Abéguilé, Geneviève3
  • Mittre, Hervé5
  • Richard, Nicolas6
  • Eckart, Philippe7
  • Castanet, Mireille8
  • Kottler, Marie-Laure9
  • 1 CHU de Caen, Department of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Caen, F-14000, France; Université Caen Normandie, Medical School, Caen, F14000, France; BioTARGEN, Université Caen Normandie, Caen, F14000, France. Electronic address: [email protected] , (France)
  • 2 Université Caen Normandie, Medical School, Caen, F14000, France; CHU de Caen, Department of Biochemistry, Caen, F-14000, France. , (France)
  • 3 CHU de Caen, Department of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Caen, F-14000, France. , (France)
  • 4 BioTARGEN, Université Caen Normandie, Caen, F14000, France. , (France)
  • 5 CHU de Caen, Department of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Caen, F-14000, France; Université Caen Normandie, Medical School, Caen, F14000, France; OeReCa, Université Caen Normandie, Caen, F14000, France. , (France)
  • 6 CHU de Caen, Department of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Caen, F-14000, France; BioTARGEN, Université Caen Normandie, Caen, F14000, France. , (France)
  • 7 CHU de Caen, Department of Pediatrics, Caen, F-14000, France. , (France)
  • 8 CHU de Rouen, Department of Pediatrics, Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Rouen, F-76000, France; Université Rouen Normandie, Medical School, Rouen, F-76000, France; INSERM U982, Laboratory of Differentiation & Neuronal and Neuroendocrine Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, Mont-Saint-Aignan, F-76130, France. , (France)
  • 9 CHU de Caen, Department of Genetics, Molecular Genetics Laboratory and Reference Center for Rare Diseases of Calcium and Phosphorus Metabolism, Caen, F-14000, France; Université Caen Normandie, Medical School, Caen, F14000, France; BioTARGEN, Université Caen Normandie, Caen, F14000, France. , (France)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Nov 01, 2019
Volume
62
Issue
11
Pages
103577–103577
Identifiers
DOI: 10.1016/j.ejmg.2018.11.011
PMID: 30423445
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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