Affiliations: Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy | Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy
Note: [] Corresponding author: Dr. Monica Mottes, PhD, Professor of Applied Biology, Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie, 8 37134 Verona, Italy. Tel.: +390458027184; Fax: +390458027180; E-mail: monica.mottes@univr.it
Abstract: Recent studies have identified the molecular defect underlying autosomal dominant osteogenesis imperfecta (OI) type V. Unlike all other OI types, which are characterized by high genetic heterogeneity, OI type V appears consistently associated to a unique de novo C>T transition within the 5′ UTR of the IFITM5 gene. Although the precise frequency of OI type V is not known, this recurrent base substitution may well represent a mutational hotspot in the human genome. We show that it occurs at a CpG dinucleotide that is highly methylated in several tissues and particularly in the sperm DNA, suggesting a mutational mechanism common to other de novo recurrent dominant mutations.
Keywords: Osteogenesis imperfecta, IFITM5, DNA methylation, CpG dinucleotide deamination
