Patient reports: Two novel frameshift mutations in the SOX9 gene in two patients with campomelic dysplasia who showed long-term survival

J Pediatr Endocrinol Metab. 2010 Nov;23(11):1189-93. doi: 10.1515/jpem.2010.187.

Abstract

Campomelic dysplasia (CD) is a rare and usually fatal congenital skeletal disorder with respiratory failure. The SOX9 gene has been cloned as a candidate gene for CD. Here, we report the cases of 2 Japanese patients with CD who have survived for over 5 years. Molecular investigations revealed novel frameshift mutations in SOX9 in these patients; a single G insertion in 1 allele at nucleotide 261 (261-262insG) and a single C insertion in 1 allele at nucleotide 888 (888-889insC). The predicted protein of 261-262insG may lack more than 80% composition of the normal SOX9 protein, including the SRY high mobility group (HMG) domain and the transactivation (TA) domain; the predicted protein of 888-889insC may not contain the normal TA domain. Although it has been reported that most patients with CD die during the neonatal period, our patients have survived for a long time, despite putative severely impaired SOX9 proteins.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Campomelic Dysplasia / genetics*
  • Child, Preschool
  • Female
  • Frameshift Mutation*
  • Humans
  • Male
  • SOX9 Transcription Factor / genetics*
  • Survivors

Substances

  • SOX9 Transcription Factor
  • SOX9 protein, human