title: A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta.
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 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.
authors: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors: Michael
authors: M
authors: Volodarsky
authors: Barak
authors: B
authors: Markus
authors: Idan
authors: I
authors: Cohen
authors: Orna
authors: O
authors: Staretz-Chacham
authors: Hagit
authors: H
authors: Flusser
authors: Daniella
authors: D
authors: Landau
authors: Ilan
authors: I
authors: Shelef
authors: Yshaia
authors: Y
authors: Langer
authors: Ohad S
authors: OS
authors: Birk
mesh_terms: D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D003241:Consanguinity; D023061:Gene Order; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007473:Ion Channels / Q000235:genetics*; D007557:Israel; D008297:Male; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D007473:Ion Channels; C578840:TMEM38B protein, human