European Journal of Pediatrics

, Volume 154, Issue 2, pp 123–129 | Cite as

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

  • Michael Raghunath
  • Katrina Mackay
  • Raymond Dalgleish
  • Beat Steinmann
Medical Genetics Original Paper


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 α2(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.

Key words

Osteogenesis imperfecta Collagen I Mosaicism Genetics Recurrence risk 



osteogenesis imperfecta


polymerase chain reaction


single strand conformation polymorphism


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Michael Raghunath
    • 1
  • Katrina Mackay
    • 2
  • Raymond Dalgleish
    • 2
  • Beat Steinmann
    • 1
  1. 1.Division of Metabolism, Department of PaediatricsUniversity of ZürichZürichSwitzerland
  2. 2.Department of GeneticsUniversity of LeicesterLeicesterUK

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