Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a case report

BMC Musculoskeletal Disorders

Case Report

Jiyeon Kim¹  Myungshin Kim²  Hyojin Chae²  Hae-il Park³  Jae Young Lee⁴  Changhoon Jeong⁴  Ok-Hwa Kim⁵  Jongsun Jung⁶  Paul Kim⁶  Young Kee Lee⁶ 

[1] Catholic Genetic Laboratory Center, Seoul St. Mary’ Hospital, The Catholic University of Korea, Seoul, South Korea;Catholic Genetic Laboratory Center, Seoul St. Mary’ Hospital, The Catholic University of Korea, Seoul, South Korea;Department of Laboratory Medicine, The Catholic University of Korea, Seoul, South Korea;Department of Laboratory Medicine, The Catholic University of Korea, Seoul, South Korea;Department of Orthopaedic Surgery, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea;Department of Radiology, Ajou University Hospital, Suwon, South Korea;Syntekabio Inc, Seoul, South Korea;

关键词: Multiple epiphyseal dysplasia;    COL9A3;    Molecular dynamics simulation;   

DOI  :  10.1186/1471-2474-15-371

 received in 2014-05-13, accepted in 2014-10-23,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMultiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia.Case presentationA 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband’s x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G > A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be detelerious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX.ConclusionSo far, three COL9A3 mutations, have been reported. These three mutations are located at the splice donor or acceptor site of COL9A3 and cause skipping of exon 3, resulting in the deletion of 12 aminoacids in the COL3 domain of COL9A3. In contrast, the novel missense mutation identified in this two-generation family with multiple epiphyseal dysplasia is a missense mutation affecting the Gly residue of the Pro-Pro-Gly repeat sequence in the COL3 domain of collage IX, with accompanying major structural change of the collagen peptide.

【 授权许可】

Unknown   
© Jeong et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.