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Horm Res Paediatr. 2014;82(3):206-12. doi: 10.1159/000362618. Epub 2014 Jul 23.

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.

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1
Third Department of Pediatrics, Athens University Medical School, 'Attikon' University General Hospital, Athens, Greece.

Abstract

BACKGROUND/AIMS:

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.

PMID:
25060608
DOI:
10.1159/000362618
[Indexed for MEDLINE]
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