The use of whole exome sequencing for the diagnosis of autosomal recessive malignant infantile osteopetrosis

Clin Genet. 2017 Jul;92(1):80-85. doi: 10.1111/cge.12804. Epub 2016 Jun 2.

Abstract

Autosomal recessive malignant infantile osteopetrosis is a congenital disease characterized by pathologically increased bone density. Recently, the use of whole exome sequencing has been utilized as a clinical diagnostic tool in a number of Mendelian disorders. In this study, whole exome sequencing (WES) was successfully used in six patients with malignant infantile osteopetrosis (MIOP) and identified mutations in four MIOP-related genes (CLCN7, TCIRG1, SNX10, and TNFRSF11A). We report these patients, describe the mutations and review the current literature.

Keywords: genetic research; osteoclasts; osteopetrosis; whole exome sequencing.

MeSH terms

  • Bone Density / genetics
  • Child, Preschool
  • Chloride Channels / genetics*
  • Exome
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Osteopetrosis / genetics*
  • Osteopetrosis / physiopathology
  • Receptor Activator of Nuclear Factor-kappa B / genetics*
  • Sorting Nexins / genetics*
  • Vacuolar Proton-Translocating ATPases / genetics*

Substances

  • CLCN7 protein, human
  • Chloride Channels
  • Receptor Activator of Nuclear Factor-kappa B
  • SNX10 protein, human
  • Sorting Nexins
  • TCIRG1 protein, human
  • TNFRSF11A protein, human
  • Vacuolar Proton-Translocating ATPases