Variable expressivity of osteogenesis imperfecta in a Brazilian family due to p.G1079S mutation in the COL1A1 gene

Osteogenesis imperfecta (OI) is a Mendelian disease with genetic heterogeneity characterized by bone fragility, recurrent fractures, blue sclerae, and short stature, caused mostly by mutations in COL1A1 or COL1A2 genes, which encode the pro-alpha 1(I) and pro-alpha 2(I) chains of type I collagen, respectively. A Brazilian family that showed variable expression of autosomal dominant OI was identified and characterized. Scanning for mutations was carried out using SSCP and DNA sequence analysis. The missense mutation c.3235G>A was identified within exon 45 of the COL1A1 gene in a 16-year-old girl diagnosed as having OI type I; it resulted in substitution of a glycine residue (G) by a serine (S) at codon 1079 (p.G1079S). The proband's mother had the disease signs, but without bone fractures, as did five of nine uncles and aunts of the patient. All of them carried the mutation, which was excluded in four healthy brothers of the patient's mother. This is the first description in a Brazilian family with OI showing variable expression; only one among seven carriers for the c.3235G>A mutation developed bone fractures, the most striking clinical feature of this disease. This finding has a significant implication for prenatal diagnosis in OI disease.

Brazilian institutions ArcelorMittal Tubarao

Brazilian institutions ArcelorMittal Tubarao

Fundacao de Apoio ao Hospital Universitario Cassiano Antonio Moraes

Fundacao de Apoio ao Hospital Universitario Cassiano Antonio Moraes

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Fundo de Apoio a Ciencia e Tecnologia de Vitoria

Fundo de Apoio a Ciencia e Tecnologia de Vitoria

Fundacao de Amparo a Pesquisa do Espirito Santo

Fundacao de Amparo a Pesquisa do Espirito Santo