The recurrent causal mutation for osteogenesis imperfecta type V occurs at a highly methylated CpG dinucleotide within the IFITM5 gene.
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.
Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy.
Massimiliano
M
Corradi
Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy.
Elena
E
Monti
Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy.
Giacomo
G
Venturi
Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy.
Alberto
A
Gandini
Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
Monica
M
Mottes
Department of Life and Reproduction Sciences, Section of Pediatrics, University of Verona, Verona, Italy.
Franco
F
Antoniazzi
CpG dinucleotide deamination; DNA methylation; IFITM5; Osteogenesis imperfecta