Critical consequences of finding three pathogenic mutations in an individual with recessive disease

Sally Halsall (1) , Gemma Thornton (2) , Adeline Nicholas (2) , Howard Martin (1) , Christopher Woods (2)

1 Addenbrooke's Hospital
2 CAM - University of Cambridge [UK]

We report the unexpected finding of three different nonsense mutations in two unrelated individuals with a classical autosomal recessive disease; that is one in which two pathogenic mutations in trans are expected. This finding of ‘triple pathogenic mutations' appears to be a rare phenomena1, for which we can find no guiding literature for incidence, mechanism or consequence; however they have been reported previously in the recessive disorders Insensitivity to Pain with Anhidrosis due to TRKA mutations (OMIM 256800) and Gaucher disease due to GDI mutations (OMIM 230800). For mutation analysis in research or clinical settings such findings can have significant implications, whilst for genetic counsellinggenetic counselling the consequences can be profound.

Mots clés: Clinical genetics; Molecular genetics

Sally Halsall, Gemma Thornton, Adeline Nicholas, Howard Martin, Christopher Woods. Critical consequences of finding three pathogenic mutations in an individual with recessive disease. Journal of Medical Genetics, 2010, 47 (11), pp.769. ⟨10.1136/jmg.2010.079277⟩. ⟨hal-00557401⟩