title: Identification of a novel nonsense mutation in the ligand-binding domain of the vitamin d receptor gene and clinical description of two greek patients with hereditary vitamin d-resistant rickets and alopecia.
abstract: OBJECTIVE
  We analyzed the vitamin D receptor (VDR) gene in 2 Greek patients who exhibited the classical features of hereditary vitamin D-resistant rickets (HVDRR) type II, including severe bone deformities and alopecia. We also describe the clinical phenotypes and the response to treatment of our patients.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood samples of both patients. Coding region and flanking introns of VDR gDNA was amplified and direct sequenced.
  
  
  RESULTS
  A unique cytosine to thymine (C>T) transition was identified at nucleotide position 1066 (c.1066C>T) in the ligand-binding domain of the VDR gene of both patients, predicting the substitution of a glutamine to a terminal codon at position 356 (Gln356stop).
  
  
  CONCLUSIONS
  The novel nonsense mutation c.1066C>T (Gln356stop) is expected to result in a VDR protein 71 amino acids shorter and thus to affect the normal VDR function. In particular, the missing protein part alters the VDR heterodimerization with the retinoid X receptor which has been correlated with the presence of alopecia. Both patients were introduced to treatment with supraphysiological doses of 1α-calcidiol which improved their clinical phenotypes except for alopecia.
authors: Third Department of Pediatrics, Athens University Medical School, 'Attikon' University General Hospital, Athens, Greece.
authors: Anna
authors: A
authors: Papadopoulou
authors: Evangelia
authors: E
authors: Bountouvi
authors: Evangelia
authors: E
authors: Gole
authors: Artemis
authors: A
authors: Doulgeraki
authors: Symeon
authors: S
authors: Tournis
authors: Anastasios
authors: A
authors: Papadimitriou
authors: Polyxeni
authors: P
authors: Nicolaidou
mesh_terms: D000328:Adult; D000505:Alopecia / Q000235:genetics* / Q000503:physiopathology*; D019943:Amino Acid Substitution / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005973:Glutamine / Q000235:genetics; D006801:Humans; D018908:Muscle Weakness / Q000235:genetics / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000235:genetics*; D063730:Rickets, Hypophosphatemic / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D018389:Codon, Nonsense; D018167:Receptors, Calcitriol; D005973:Glutamine; D004247:DNA