title: Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes.
abstract: BACKGROUND
  Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. Variable phenotypes have been associated with these mutations, and some of these were linked to the effects they have on the interacting partners of VDR, mainly the retinoic X receptor (RXR).
  
  
  METHODS
  We examined four patients with HVDRR from three unrelated Lebanese families. All parents were consanguineous with normal phenotype. We used Sanger sequencing to identify mutations in the coding exons of VDR.
  
  
  RESULTS
  Two homozygous mutations (p.R391S and p.H397P), both in exon 9 of the VDR gene, were identified. Phenotype/genotype association was not possible even for the same mutation. Alopecia was seen only with the p.R391S mutation. Despite a comparable rachitic bone disease, the patients showed different responsiveness to large doses of alfacalcidol (1-α-hydroxy vitamin D3) supplementation.
  
  
  CONCLUSIONS
  This is the first report of VDR mutations in Lebanon with promising clinical outcomes despite the severity of the phenotypes.
authors.affiliation: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut.
authors.forename: Rabih
authors.initials: R
authors.lastname: Andary
authors.affiliation: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut.
authors.forename: Abdul-Karim
authors.identifier: http://orcid.org/0000-0002-4017-4908
authors.initials: AK
authors.lastname: El-Hage-Sleiman
authors.affiliation: Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut.
authors.forename: Theresa
authors.initials: T
authors.lastname: Farhat
authors.affiliation: Department of Pediatrics and Adolescent Medicine, American University of Beirut, Bliss Street, Beirut.
authors.forename: Sami
authors.initials: S
authors.lastname: Sanjad
authors.affiliation: Department of Biochemistry and Molecular Genetics, American University of Beirut, Bliss Street P.O. Box 11-0236, Beirut.
authors.forename: Georges
authors.identifier: http://orcid.org/0000-0003-2157-5279
authors.initials: G
authors.lastname: Nemer
mesh_terms: D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D007223:Infant; D007861:Lebanon / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human
keywords: alopecia; genetics; mutation; receptor; vitamin D