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
