Genetic counselling on brittle grounds: recurring osteogenesis imperfecta due to parental mosaicism for a dominant mutation

Abstract

Osteogenesis imperfecta (OI), a dominantly inherited connective tissue disorder, is usually caused by defects in collagen I. There is growing evidence for parental mosaicism that results in affected children born to unaffected parents. This situation poses a difficult task for the geneticist because a mosaic parent may appear clinically healthy while carrying the mutation in a fraction of her or his gonadal cells. To illustrate this problem, we report a Swiss couple whose first child was affected with severe OI. The unexpected recurrence of the disorder in the second child raised the suspicion of a recessive trait or, rather, of parental mosaicism. We identified the responsible collagen mutation in the COL1A2 gene (Gly688Ser in the alpha 2(I)-chain) in both children and demonstrated the father to be a somatic mosaic for this mutation and to have subtle clinical signs such as soft skin and short stature that may be a result of his mosaic state.

Conclusion: After the birth of a child affected with OI the possibility of parental mosaicism should be considered and options for prenatal diagnosis discussed.