The 22q11.2 deletion is the most prominent known genetic risk factor for
schizophrenia, but its penetrance is at most approximately 50% suggesting
that additional risk factors are required for disease progression. We
examined a woman with schizophrenia with this deletion for such risk
factors. She had high plasma pentosidine levels (‘carbonyl stress’) and a
frameshift mutation in the responsible gene, GLO1. She also
had a constant exotropia, so we examined the PHOX2B gene
associated with both schizophrenia and strabismus, and detected a 5-alanine
deletion. We propose that the combination of these genetic defects may have
exceeded the threshold for the manifestation of schizophrenia.