TY - JOUR
T1 - Mutation of GPR143 Associated With Ocular Albinism Type 1, Intellectual Disability, and Schizophrenia
T2 - The Complex Biological and Social Interactions Between Genetic Syndromes and Mental Illness
AU - Arcadepani, Felipe B.
AU - Gadelha, Ary
AU - Margolis, Russell L.
N1 - Funding Information:
Supported by the ABCD Charitable Trust.
Publisher Copyright:
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/1/5
Y1 - 2023/1/5
N2 - 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.
AB - 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.
KW - copy number variation
KW - deletion
KW - genetic syndrome
KW - ocular albinism
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85146404211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146404211&partnerID=8YFLogxK
U2 - 10.1097/PRA.0000000000000685
DO - 10.1097/PRA.0000000000000685
M3 - Article
C2 - 36649556
AN - SCOPUS:85146404211
SN - 1527-4160
VL - 29
SP - 77
EP - 81
JO - Journal of psychiatric practice
JF - Journal of psychiatric practice
IS - 1
ER -