期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 91, 期 2, 页码 343-348出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2012.06.005
关键词
-
资金
- Bio & Medical Technology Development Program [2011-0027790]
- Science Research Center grant of the National Research Foundation (NRF) [2012-0000487]
- Korean government (MEST)
- Korea Healthcare Technology Research and Development Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea [A080588]
- National Research Foundation of Korea [2006-2005219, 2008-0062460, 전06A1202] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据