Osteogenesis Imperfecta (OI) is characterized by bone fractures with minimal or no trauma, dentinogenesis imperfecta (DI) and hearing loss in adults. Fractures may occur in any bone, but most often of the limbs.
The clinical features of OI, associated with mutations in the COL1A1 (OMIM 120150) & COL1A2 (OMIM 120160) genes, represent a range that includes perinatal mortality in patients with severe skeletal deformities, mobility problems and very short stature, while there are also individuals with mutations in one of the two genes who are virtually asymptomatic or with a mild predisposition to fractures and a normal stature and life.
Osteogenesis Imperfecta is classified into four types (I, II, III, and IV) based on clinical and radiological findings. This classification scheme may be useful to provide information regarding disease prognosis and management in affected individuals.
The four types of OI are referred to as:
- OI type Ι: classic, non-deforming type
- OI type II: perinatally lethal
- OI type ΙΙΙ: progressively deforming
- OI type IV: common, variable type
Diagnosis is based on radiographic findings and also on genetic testing of the COL1A1 & COL1A2 genes, two relatively large in size genes with several mutations. Both OI types are inherited in an autosomal dominant manner and most mutations in patients are de novo, i.e. not inherited from a parent.
We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the COL1A1 & COL1A2 genes, allowing us to detect, through the use of specially developed bioinformatics tools, >98% of all pathogenic mutations of the genes and the associated syndromes.
Where possible and/or necessary, we carry out additional MLPA analysis in order to detect deletions/duplications of the genes (please consult the final test report).
The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.
Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.