Osteogenesis imperfecta: clinical, biochemical and molecular findings.
Mutations in COL1A1 and COL1A2 genes, encoding the alpha1 and alpha2 chain of type I collagen, respectively, are responsible for the vast majority of cases of osteogenesis imperfecta (OI) (95% of patients with a definite clinical diagnosis). We have investigated 22 OI patients, representing a heterogeneous phenotypic range, at the biochemical and molecular level. A causal mutation in either type I collagen gene was identified in 20 of them: no recurrent mutation was found in unrelated subjects; 15 out of 20 mutations had not been reported previously. In two patients, we could not find any causative mutation in either type I collagen gene, after extensive genomic DNA sequencing. Failure of COL1A1/COL1A2 mutation screening may be due, in a few cases, to further clinical heterogeneity, i.e. additional non-collagenous disease loci are presumably involved in OI types beyond the traditional Sillence's classification.
Venturi
G
G
Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy.
Tedeschi
E
E
Mottes
M
M
Valli
M
M
Camilot
M
M
Viglio
S
S
Antoniazzi
F
F
Tatò
L
L
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D003094:Collagen