Two siblings with a novel nonsense mutation, p.R50X, in the vitamin D receptor gene

Endocrine. 2011 Aug;40(1):62-6. doi: 10.1007/s12020-011-9450-9. Epub 2011 Mar 18.

Abstract

Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disorder caused by inactivating mutations in the vitamin D receptor (VDR) gene. We identified two affected children from the same family, one at the age of 10 years and 9 months and the other at 9 months old. Mutation analysis by PCR-sequencing the entire coding region of the VDR gene revealed a homozygous C to T transition in exon 2 of the VDR gene (c.148C>T) resulting in a stop codon at amino acid position 50 (p.R50X) in the proband and his younger sister. The p.R50X has never been previously described. Both asymptomatic parents were heterozygous for the mutation. In addition to most of the clinical features of HVDRR including total alopecia, symptoms of hypocalcemia at a later onset and normophosphatemia, rarely found in HVDRR were present in the proband. This study also emphasizes an important role of genetic testing for early diagnosis and genetic counseling.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / diagnosis
  • Alopecia / genetics
  • Child
  • Codon, Nonsense / genetics*
  • DNA Mutational Analysis
  • Familial Hypophosphatemic Rickets / diagnosis
  • Familial Hypophosphatemic Rickets / genetics*
  • Genetic Counseling
  • Genetic Testing
  • Homozygote*
  • Humans
  • Infant
  • Male
  • Receptors, Calcitriol / genetics*
  • Siblings

Substances

  • Codon, Nonsense
  • Receptors, Calcitriol