A Deletion Mutation in TMEM38B Associated with Autosomal Recessive Osteogenesis Imperfecta

Michael Volodarsky, Barak Markus, Idan Cohen, Orna Staretz-Chacham, Hagit Flusser, Daniella Landau, Ilan Shelef, Yshaia Langer, Ohad S. Birk

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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 Ca2+ 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. We demonstrate through homozygosity mapping and whole exome seuquencing that autosomal recessive osteogensis imperfecta (OI) type IV is associated with a homozygous deletion mutation of exon 4 of TMEM38B. TMEM38B encodes TRIC-B, a ubiquitous component of TRIC, a monovalent cation-specific channel involved in Ca2+ release from intracellular stores that has been shown to act in cell differentiation.

Original languageEnglish
Pages (from-to)582-586
Number of pages5
JournalHuman Mutation
Volume34
Issue number4
DOIs
StatePublished - 1 Apr 2013

Keywords

  • Homozygosity mapping
  • Osteogenesis imperfecta
  • TMEM38B
  • TRIC-B

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