이숙경 (서울대학교) | 한빛사논문 > 한빛사

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이숙경Sook-Kyung Lee

서울대학교

Am. J. Hum. Genet., Volume 91, Issue 2, 343-348, 02 August 2012 | doi:10.1016/j.ajhg.2012.06.005 A Single Recurrent Mutation in the 5-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V

Abstract

Tae-Joon Cho^{1, 10, *}, Kyung-Eun Lee^{2, 5, 10}, Sook-Kyung Lee^{2, 5, 10}, Su Jeong Song^{2, 5}, Kyung Jin Kim^{2, 5}, Daehyun Jeon^{3, 5}, Gene Lee^{3, 5}, Ha-Neui Kim^{4, 5}, Hye Ran Lee¹, Hye-Hyun Eom⁶, Zang Hee Lee^{4, 5}, Ok-Hwa Kim⁷, Woong-Yang Park⁶, Sung Sup Park⁸, Shiro Ikegawa⁹, Won Joon Yoo¹, In Ho Choi¹ and Jung-Wook Kim^{2, 3, 5, *}

¹ Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul 110-744, Republic of Korea
² Department of Pediatric Dentistry, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
³ Department of Molecular Genetics, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
⁴ Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
⁵ Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
⁶ Departments of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea
⁷ Department of Radiology, Ajou University Hospital, Suwon 443-721, Republic of Korea
⁸ Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea
⁹ Laboratory of Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo108-8639, Japan

^*Corresponding author : Tae-Joon Cho
^*Corresponding author : Jung-Wook Kim

¹⁰ These authors contributed equally to this work.

Abstract
Osteogenesis imperfecta (OI) is a heterogenous group of genetic disorders of bone fragility. OI type V is an autosomal-dominant disease characterized by calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation; the causative mutation involved in this disease has not been discovered yet. Using linkage analysis in a four-generation family and whole-exome sequencing, we identified a heterozygous mutation of c.14C>T in the 5-untranslated region of a gene encoding interferon-induced transmembrane protein 5 (IFITM5). It completely cosegregated with the disease in three families and occurred de novo in five simplex individuals. Transfection of wild-type and mutant IFITM5 constructs revealed that the mutation added five amino acids (Met-Ala-Leu-Glu-Pro) to the N terminus of IFITM5. Given that IFITM5 expression and protein localization is restricted to the skeletal tissue and IFITM5 involvement in bone formation, we conclude that this recurrent mutation would have a specific effect on IFITM5 function and thus cause OI type V.

논문정보

형식Research article
게재일2012년 08월 (BRIC 등록일 )
연구진국내(교신)+국외 연구진
분야 의약학 > 유전 및 유전체의학
피인용횟수120회 이상 인용된 논문 (상위피인용논문 등록일 2019-04-11)

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