Mutation of GPR143 Associated With Ocular Albinism Type 1, Intellectual Disability, and Schizophrenia: The Complex Biological and Social Interactions Between Genetic Syndromes and Mental Illness

Abstract

Copy number variations, which manifest primarily as deletions and duplications, contribute significantly to the genetic risk of schizophrenia. Specific syndromes associated with copy number variations, exemplified by the 22q11 deletion syndrome, confer both congenital abnormalities and an elevated risk of schizophrenia. We report the case of a patient with a deletion of exons 2 through 8 of GPR143. In addition to having the ophthalmologic disorder ocular albinism type 1 (OA1), a well-established consequence of mutations of GPR143, the patient is also intellectually impaired and impulsive, and he developed schizophrenia at age 15. Psychiatric manifestations of OA1 have not previously been reported, yet remain plausible, as the GPR143 protein is widely distributed in the brain and may function as an L-DOPA receptor. However, the patient described here also had a family history of psychiatric disorders independent of OA1, in utero exposure to heroin and cocaine, and challenging family circumstances. We suggest that the relationship between his GPR143 mutation and his psychiatric disorders is complex. The mutation may have directly contributed to his cognitive and psychiatric disorders, but we also suspect that OA1, present in multiple family members, contributed to multigenerational familial instability. Further, OA1 likely exacerbated our patient's cognitive and social impairment by interfering with his education, while his neuropsychiatric status frequently interfered with the assessment and treatment of his OA1. We conclude that the psychiatric and nonpsychiatric manifestations of a genetic syndrome are best managed in parallel and that psychiatrists and other mental health providers may be in the best position to assure that patients receive appropriate genetic and medical care.