首页 | 本学科首页   官方微博 | 高级检索  
   检索      


The molecular defect in a family with mild atypical osteogenesis imperfecta and extreme joint hypermobility: Exon skipping caused by an 11-bp deletion from an intron in one COL1A2 allele
Authors:A C Nicholls  J Oliver  D V Renouf  D A Heath  F M Pope
Institution:(1) Dermatology Research Group, Clinical Research Centre, Watford Road, HAI 3UJ Harrow, UK;(2) Department of Medicine, Queen Elizabeth Hospital, University of Birmingham, B15 2TH Edgbaston, Birmingham, UK;(3) Present address: Glycoconjugates Research Section, Clinical Research Centre, HAI 3UJ Harrow, UK
Abstract:Summary We have investigated a family with an autosomal dominantly inherited connective-tissue defect causing extreme joint hypermobility, premature osteoporosis and late-onset fractures. Analysis of collagenous proteins from affected individuals showed a deletion in some agr2(I) chains. Peptide mapping localized this to the CB peptide agr2CB4, which covers the N-terminal one-third of the protein chain. Polymerase chain reaction amplification and sequencing of cDNA derived from this region of the mRNA identified á heterozygous deletion of the 54 by comprising exon 9. Similar analysis of the genomic DNA revealed an 11-bp deletion from bp3 to bp13 of IVS-9. This disrupts the consensus 5prime splice signal (GTAAGT) and leads to exon skipping. In a family study of 13 affected and unaffected family members using both heteroduplex formation and direct analysis for the deletion, all of the affected, but no unaffected individuals, were found to carry the deletion. This generated a positive Lod score of 2.6 with the Liped programme.
Keywords:
本文献已被 SpringerLink 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号