Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation

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 c...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of medical genetics Vol. 49; no. 10; p. 630
Main Authors:	Shaheen, Ranad, Alazami, Anas M, Alshammari, Muneera J, Faqeih, Eissa, Alhashmi, Nadia, Mousa, Noon, Alsinani, Aisha, Ansari, Shinu, Alzahrani, Fatema, Al-Owain, Mohammed, Alzayed, Zayed S, Alkuraya, Fowzan S
Format:	Journal Article
Language:	English
Published:	England 01-10-2012
Subjects:	Arabia Base Sequence Collagen Type I - genetics Consanguinity Exons Female Gene Order Genes, Recessive Homozygote Humans Infant Infant, Newborn Ion Channels - genetics Male Mutation Osteogenesis Imperfecta - diagnosis Osteogenesis Imperfecta - genetics Arabia
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. 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. 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. 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.
ISSN:	1468-6244
DOI:	10.1136/jmedgenet-2012-101142