Communicated by Raymond Dalgleish
A Deletion Mutation in TMEM38B Associated with Autosomal Recessive Osteogenesis Imperfecta
Article first published online: 20 MAR 2013
© 2013 Wiley Periodicals, Inc.
Volume 34, Issue 4, pages 582–586, April 2013
How to Cite
Volodarsky, M., Markus, B., Cohen, I., Staretz-Chacham, O., Flusser, H., Landau, D., Shelef, I., Langer, Y. and Birk, O. S. (2013), A Deletion Mutation in TMEM38B Associated with Autosomal Recessive Osteogenesis Imperfecta. Hum. Mutat., 34: 582–586. doi: 10.1002/humu.22274
Contract grant sponsors: Israel Science Foundation (ISF grant 1689/12); the Kahn Foundation.
- Issue published online: 20 MAR 2013
- Article first published online: 20 MAR 2013
- Accepted manuscript online: 12 JAN 2013 10:26PM EST
- Manuscript Accepted: 4 JAN 2013
- Manuscript Received: 24 OCT 2012
- Israel Science Foundation. Grant Number: 1689/12
- The Kahn Foundation
- osteogenesis imperfecta;
- homozygosity mapping
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.