A Deletion Mutation in TMEM38B Associated with Autosomal Recessive Osteogenesis Imperfecta

作者：Volodarsky Michael; Markus Barak; Cohen Idan; Staretz Chacham Orna; Flusser Hagit; Landau Daniella; Shelef Ilan; Langer Yshaia; Birk Ohad S^*

来源：Human Mutation, 2013, 34(4): 582-586.

DOI：10.1002/humu.22274

• osteogenesis imperfecta
• TMEM38B
• TRIC-B
• 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 2Mb 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.

• 出版日期2013-4