RT Journal Article SR Electronic T1 Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 630 OP 635 DO 10.1136/jmedgenet-2012-101142 VO 49 IS 10 A1 Ranad Shaheen A1 Anas M Alazami A1 Muneera J Alshammari A1 Eissa Faqeih A1 Nadia Alhashmi A1 Noon Mousa A1 Aisha Alsinani A1 Shinu Ansari A1 Fatema Alzahrani A1 Mohammed Al-Owain A1 Zayed S Alzayed A1 Fowzan S Alkuraya YR 2012 UL http://jmg.bmj.com/content/49/10/630.abstract AB Background Osteogenesis imperfecta (OI) is an hereditary bone disease in which increased bone fragility leads to frequent fractures and other complications, usually in an autosomal dominant fashion. An expanding list of genes that encode proteins related to collagen metabolism are now recognised as important causes of autosomal recessive (AR) OI. Our aim was to study the contribution of known genes to AR OI in order to identify novel loci in mutation-negative cases. Methods We enrolled multiplex consanguineous families and simplex cases (also consanguineous) in which mutations in COL1A1 and COL1A2 had been excluded. We used autozygome guided mutation analysis of AR OI (AR OI) genes followed by exome sequencing when such analysis failed to identify the causative mutation. Results Two simplex and 11 multiplex families were enrolled, encompassing 27 cases. In three multiplex families, autozygosity and linkage analysis revealed a novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating deletion of exon 4 of TMEM38B was identified within that interval. In addition, gonadal or gonadal/somatic mosaic mutations in COL1A1 or COL1A2 and homozygous mutations in recently described AR OI genes were identified in all remaining families. Conclusions TMEM38B is a novel candidate gene for AR OI. Future studies are needed to explore fully the contribution of this gene to AR OI in other populations.