Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects

Am J Hum Genet. 2011 Dec 9;89(6):773-81. doi: 10.1016/j.ajhg.2011.11.002.

Abstract

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression of three major odontogenesis genes: dlx2, bmp2, and pitx2.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics*
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 6
  • Consanguinity
  • Dentin Dysplasia / diagnosis
  • Dentin Dysplasia / genetics*
  • Exome*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Genetic Association Studies
  • Homozygote*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Pedigree
  • Sequence Analysis, DNA*
  • Tooth / growth & development*
  • Zebrafish / genetics
  • Zebrafish / growth & development

Substances

  • Calcium-Binding Proteins
  • Carrier Proteins
  • DACT2 protein, human
  • Neoplasm Proteins
  • SMOC2 protein, human

Associated data

  • GENBANK/JQ085591