A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta

Hum Mutat. 2013 Apr;34(4):582-6. doi: 10.1002/humu.22274.


Autosomal recessive osteogenesis imperfecta (OI) was diagnosed in three unrelated Israeli Bedouin consanguineous families. Fractures were evident in all cases in infancy. Genome-wide linkage analysis ruled out association with any of the known OI genes, and identified a single homozygosity locus of approximately 2 Mb on chromosome 9 common to all affected individuals (maximum multipoint lod score 6.5). Whole exome sequencing identified only a single mutation within this locus that was shared by all affected individuals: a homozygous deletion mutation of exon 4 of TMEM38B, leading to an early stop codon and a truncated protein, as well as low TMEM38B mRNA levels. TMEM38B encodes TRIC-B, a ubiquitous component of TRIC, a monovalent cation-specific channel involved in Ca(2+) release from intracellular stores that has been shown to act in cell differentiation. Molecular mechanisms through which a TMEM38B mutation might lead to an OI phenotype are yet to be explored.

Publication types

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

MeSH terms

  • Adult
  • Base Sequence
  • Child, Preschool
  • Consanguinity
  • Gene Order
  • Genes, Recessive*
  • Genetic Association Studies
  • Humans
  • Infant
  • Ion Channels / genetics*
  • Israel
  • Male
  • Osteogenesis Imperfecta / diagnosis*
  • Osteogenesis Imperfecta / genetics*
  • Pedigree
  • Sequence Deletion*


  • Ion Channels
  • TMEM38B protein, human