Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta
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- 作者：Yasemin Alanay ; Hrispima Avaygan ; Natalia Camacho ; G. Eda Utine ; Koray Boduroglu ; Dilek Aktas ; Mehmet Alikasifoglu ; Ergul Tuncbilek ; Diclehan Orhan ; Filiz Tiker Bakar ; Bernard Zabel ; Andrea Superti-Fu
- 刊名：The American Journal of Human Genetics
- 出版年：2010
- 出版时间：9 April 2010
- 年：2010
- 卷：86
- 期：4
- 页码：551-559
- 全文大小：1312 K
文摘
Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that results from defects in the synthesis, structure, or posttranslational modification of type I procollagen. Dominant forms of OI result from mutations in COL1A1 or COL1A2, which encode the chains of the type I procollagen heterotrimer. The mildest form of OI typically results from diminished synthesis of structurally normal type I procollagen, whereas moderately severe to lethal forms of OI usually result from structural defects in one of the type I procollagen chains. Recessively inherited OI, usually phenotypically severe, has recently been shown to result from defects in the prolyl-3-hydroxylase complex that lead to the absence of a single 3-hydroxyproline at residue 986 of the α1(I) triple helical domain. We studied a cohort of five consanguineous Turkish families, originating from the Black Sea region of Turkey, with moderately severe recessively inherited OI and identified a novel locus for OI on chromosome 17. In these families, and in a Mexican-American family, homozygosity for mutations in FKBP10, which encodes FKBP65, a chaperone that participates in type I procollagen folding, was identified. Further, we determined that FKBP10 mutations affect type I procollagen secretion. These findings identify a previously unrecognized mechanism in the pathogenesis of OI.