A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta. Academic Article uri icon

abstract

  • Autosomal recessive osteogensis 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 osteogenesis imperfecta (OI) genes, and identified a single homozygosity locus of ∼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 date

  • April 1, 2013