GENETIC-COUNSELING ON BRITTLE GROUNDS - RECURRING OSTEOGENESIS IMPERFECTA DUE TO PARENTAL MOSAICISM FOR A DOMINANT MUTATION

Osteogenesis imperfecta (OI), a dominantly inherited connective tissue disorder, is usually caused by defects in collagen I. There is growin g evidence for parental mosaicism that results in affected children bo rn to unaffected parents. This situation poses a difficult task for th e geneticist because a mosaic parent may appear clinically healthy whi le carrying the mutation in a fraction of her or his gonadal cells. To illustrate this problem, we report a Swiss couple whose first child w as affected with severe OI. The unexpected recurrence of the disorder in the second child raised the suspicion of a recessive trait or, rath er, of parental mosaicism. We identified the responsible collagen muta tion in the COL1A2 gene (Gly688Ser in the alpha 2(I)-chain) in both ch ildren and demonstrated the father to be a somatic mosaic for this mut ation and to have subtle clinical signs such as soft skin and short st ature that may be a result of his mosaic state. Conclusion After the b irth of a child affected with OI the possibility of parental mosaicism should be considered and options for prenatal diagnosis discussed.