A Single Recurrent Mutation in the 5 %26apos;-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V

作者：Cho Tae Joon; Lee Kyung Eun; Lee Sook Kyung; Song Su Jeong; Kim Kyung Jin; Jeon Daehyun; Lee Gene; Kim Ha Neui; Lee Hye Ran; Eom Hye Hyun; Lee Zang Hee; Kim Ok Hwa; Park Woong Yang; Park Sung Sup; Ikegawa Shiro; Yoo Won Joon; Choi In Ho; Kim Jung Wook^*

来源：American Journal of Human Genetics, 2012, 91(2): 343-348.

DOI：10.1016/j.ajhg.2012.06.005

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%26gt;T in the 5%26apos;-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.

• 出版日期2012-8-10