S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
A Single Recurrent Mutation in the 5'-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V.
- Issue Date
- AMERICAN JOURNAL OF HUMAN GENETICS Vol.91 No.2, pp. 343-348
- 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 50-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.
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