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

Vichit Supornsilchai1, Yodporn Hiranras, Suttipong Wacharasindhu

  • 1Division of Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Endocrine
|March 23, 2011
PubMed

Insights

Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) gene mutations. A novel p.R50X mutation was identified in two siblings, highlighting the importance of genetic testing for early diagnosis.

Area of Science:

  • Genetics
  • Endocrinology
  • Molecular Biology

Background:

  • Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder.
  • It results from inactivating mutations in the vitamin D receptor (VDR) gene.

Observation:

  • Two siblings with HVDRR were identified, aged 10 years 9 months and 9 months.
  • Mutation analysis revealed a novel homozygous C to T transition (c.148C>T) in exon 2 of the VDR gene, leading to a premature stop codon (p.R50X).
  • The proband presented with total alopecia, late-onset hypocalcemia, and normophosphatemia, symptoms not typically found in HVDRR.

Findings:

  • A novel VDR gene mutation, p.R50X, was identified in two siblings with HVDRR.
  • Both asymptomatic parents were heterozygous carriers of the mutation.
  • The identified mutation resulted in a premature stop codon in the VDR gene.

Implications:

  • This study identifies a new mutation causing HVDRR.
  • Genetic testing is crucial for early diagnosis and genetic counseling in families with HVDRR.
  • The findings contribute to understanding the genetic basis of vitamin D resistance.

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