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A Deletion Mutation in TMEM 38 B Associated with Autosomal Recessive Osteogenesis Imperfecta
Author(s) -
Volodarsky Michael,
Markus Barak,
Cohen Idan,
StaretzChacham Orna,
Flusser Hagit,
Landau Daniella,
Shelef Ilan,
Langer Yshaia,
Birk Ohad S.
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22274
Subject(s) - biology , genetics , locus (genetics) , osteogenesis imperfecta , exome sequencing , exon , phenotype , exome , disease gene identification , consanguinity , gene , mutation , anatomy
Autosomal recessive osteogenesis imperfecta ( OI ) was diagnosed in three unrelated I sraeli B edouin 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 m RNA levels. TMEM38B encodes TRIC ‐ B , a ubiquitous component of TRIC , a monovalent cation‐specific channel involved in C a 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.