Exome sequencing reveals a mutation in DMP1 in a family with familial sclerosing bone dysplasia

Marie Hélène Gannagé-Yared, Periklis Makrythanasis, Eliane Chouery, Cristina Sobacchi, Cybel Mehawej, Federico A. Santoni, Michel Guipponi, Stylianos E. Antonarakis, Hanan Hamamy, André Mégarbané

Research output: Contribution to journalArticle

Abstract

Introduction: Hypophosphatemic rickets (HR) comprises a rare group of inherited diseases. Very recently, mutations in the dentin matrix protein 1 (DMP1) gene were identified in patients with an extremely rare autosomal recessive form of HR (ARHR). To date, very few cases of these mutations were reported. Materials and methods: A Lebanese consanguineous family with 2 affected sisters was studied. Patients aged 45 and 47 years old presented with short stature, severe genu varum, cranial hyperostosis and a very high bone density that led to a diagnosis of a familial sclerosing bone dysplasia. Molecular analysis of known genes involved in osteopetrosis showed normal results. A combination of genotyping and exome sequencing was performed in order to elucidate the genetic basis of this pathology. Results: Biochemical analysis was consistent with normal serum calcium and 1-25(OH)2D levels, low to normal serum phosphorus and elevated PTH values. Serum c-terminal FGF-23 was elevated in one of the two patients. A homozygous mutation disrupting the initiation codon of the DMP1 gene (OMIM 600980), NM_001079911.2: c.1A>G, p.Met1Val, was identified by exome sequencing and confirmed by Sanger sequencing. Conclusion: We report here a family of ARHR secondary to a DMP1 mutation located in the first coding exon of the gene. Our cases show that some ARHR cases may develop with age an unaccountable increase in bone density and bone overgrowth.

Original languageEnglish
Pages (from-to)142-145
Number of pages4
JournalBone
Volume68
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • DMP1
  • Exome
  • Sclerosing bone dysplasia

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Medicine(all)

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    Gannagé-Yared, M. H., Makrythanasis, P., Chouery, E., Sobacchi, C., Mehawej, C., Santoni, F. A., Guipponi, M., Antonarakis, S. E., Hamamy, H., & Mégarbané, A. (2014). Exome sequencing reveals a mutation in DMP1 in a family with familial sclerosing bone dysplasia. Bone, 68, 142-145. https://doi.org/10.1016/j.bone.2014.08.014