Novel SOST gene mutation in a sclerosteosis patient and her parents

Bone. 2013 Feb;52(2):707-10. doi: 10.1016/j.bone.2012.10.009. Epub 2012 Oct 16.

Abstract

Introduction: Sclerosteosis (OMIM 269500) is a rare autosomal recessive condition characterized by increased bone density associated with syndactyly. It is linked to a genetic defect in the SOST gene coding for sclerostin. So far, six different loss-of-function mutations in SOST have been reported in patients with sclerosteosis. Our objective was to sequence and identify mutation in the SOST and LRP5 genes which are known to be causal for craniotubular hyperostosis in a patient from India.

Patient and methods: A 22year old woman presented with typical features of sclerosteosis in form of progressive visual and hearing loss, syndactyly and radiographs revealing increased density of bone. Genomic sequencing of the SOST gene as well as exons 2, 3 and 4 of the LRP5 gene was performed.

Results: We identified a novel homozygous mutation in the (SOST) gene, characterized as one nucleotide insertion resulting in a frame shift mutation and loss of functional sclerostin. Her parents were also found to have a similar but heterozygous mutation in the (SOST) gene.

Conclusion: A novel frame shift mutation in the (SOST) gene causing loss of functional sclerostin was identified in a patient with sclerosteosis and her parents.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Base Sequence
  • Bone Morphogenetic Proteins / chemistry
  • Bone Morphogenetic Proteins / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Humans
  • Hyperostosis / complications
  • Hyperostosis / diagnostic imaging
  • Hyperostosis / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Parents*
  • Pedigree
  • Pelvis / diagnostic imaging
  • Radiography
  • Syndactyly / complications
  • Syndactyly / diagnostic imaging
  • Syndactyly / genetics*
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human

Supplementary concepts

  • Sclerosteosis