Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review

Abstract Background Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases. Methods This review provides a comprehensive overview of RAI1’s role, integrating both clinical and basic research on Smith–Magenis syndrome (SMS) and Potocki–Lupsk...

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Main Authors: Tianmi Yang, Dejiang Pang, Chunyu Li, Huifang Shang
Format: Article
Language:English
Published: Cambridge University Press 2025-01-01
Series:Expert Reviews in Molecular Medicine
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Online Access:https://www.cambridge.org/core/product/identifier/S1462399425000122/type/journal_article
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author Tianmi Yang
Dejiang Pang
Chunyu Li
Huifang Shang
author_facet Tianmi Yang
Dejiang Pang
Chunyu Li
Huifang Shang
author_sort Tianmi Yang
collection DOAJ
description Abstract Background Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases. Methods This review provides a comprehensive overview of RAI1’s role, integrating both clinical and basic research on Smith–Magenis syndrome (SMS) and Potocki–Lupski syndrome (PTLS) while also summarising research progress on its involvement in spinocerebellar ataxia (SCA), autism spectrum disorder (ASD), schizophrenia, bipolar disorder and major depression. A systematic review of the literature was conducted using PubMed and EMBASE, following the PRISMA guidelines, with the protocol registered in PROSPERO (CRD42023474165). Results A total of 99 eligible studies on RAI1 were included. We presented detailed characterisations of SMS and PTLS patients, emphasising the crucial role of RAI1 haploinsufficiency and overexpression in their pathogenesis. Additionally, we summarised research progress on RAI1 in SCA, ASD, schizophrenia, bipolar disorder and major depression. Integrating findings from animal studies, particularly those examining the regulatory mechanisms of RAI1 in critical phenotypes, such as body weight, sleep and epilepsy, underscores the precise regulation of RAI1 expression in maintaining various nervous system functions. Conclusions Overall, this review contributes to the identification of RAI1-related neuropsychiatric diseases, with a particular emphasis on enhancing clinical diagnosis of SMS and PTLS in developing countries.
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spelling doaj-art-500e87c6cb1a441ca0d8982c8987600b2025-08-20T12:57:28ZengCambridge University PressExpert Reviews in Molecular Medicine1462-39942025-01-012710.1017/erm.2025.12Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic ReviewTianmi Yang0Dejiang Pang1Chunyu Li2Huifang Shang3https://orcid.org/0000-0003-0947-1151Department of Neurology, West China Hospital, Sichuan University, Sichuan, China Laboratory of Neurodegenerative Disorders, West China Hospital, https://ror.org/007mrxy13 Sichuan University , Sichuan, ChinaDepartment of Neurology, West China Hospital, Sichuan University, Sichuan, China Laboratory of Neurodegenerative Disorders, West China Hospital, https://ror.org/007mrxy13 Sichuan University , Sichuan, China National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, ChinaDepartment of Neurology, West China Hospital, Sichuan University, Sichuan, China Laboratory of Neurodegenerative Disorders, West China Hospital, https://ror.org/007mrxy13 Sichuan University , Sichuan, China National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, ChinaDepartment of Neurology, West China Hospital, Sichuan University, Sichuan, China Laboratory of Neurodegenerative Disorders, West China Hospital, https://ror.org/007mrxy13 Sichuan University , Sichuan, China National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, ChinaAbstract Background Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases. Methods This review provides a comprehensive overview of RAI1’s role, integrating both clinical and basic research on Smith–Magenis syndrome (SMS) and Potocki–Lupski syndrome (PTLS) while also summarising research progress on its involvement in spinocerebellar ataxia (SCA), autism spectrum disorder (ASD), schizophrenia, bipolar disorder and major depression. A systematic review of the literature was conducted using PubMed and EMBASE, following the PRISMA guidelines, with the protocol registered in PROSPERO (CRD42023474165). Results A total of 99 eligible studies on RAI1 were included. We presented detailed characterisations of SMS and PTLS patients, emphasising the crucial role of RAI1 haploinsufficiency and overexpression in their pathogenesis. Additionally, we summarised research progress on RAI1 in SCA, ASD, schizophrenia, bipolar disorder and major depression. Integrating findings from animal studies, particularly those examining the regulatory mechanisms of RAI1 in critical phenotypes, such as body weight, sleep and epilepsy, underscores the precise regulation of RAI1 expression in maintaining various nervous system functions. Conclusions Overall, this review contributes to the identification of RAI1-related neuropsychiatric diseases, with a particular emphasis on enhancing clinical diagnosis of SMS and PTLS in developing countries. https://www.cambridge.org/core/product/identifier/S1462399425000122/type/journal_articleneuropsychiatric diseasesPotocki–Lupski syndromeRAI1retinoic acid-induced 1Smith–Magenis syndromesystematic review
spellingShingle Tianmi Yang
Dejiang Pang
Chunyu Li
Huifang Shang
Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
Expert Reviews in Molecular Medicine
neuropsychiatric diseases
Potocki–Lupski syndrome
RAI1
retinoic acid-induced 1
Smith–Magenis syndrome
systematic review
title Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
title_full Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
title_fullStr Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
title_full_unstemmed Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
title_short Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review
title_sort retinoic acid induced 1 gene and neuropsychiatric diseases a systematic review
topic neuropsychiatric diseases
Potocki–Lupski syndrome
RAI1
retinoic acid-induced 1
Smith–Magenis syndrome
systematic review
url https://www.cambridge.org/core/product/identifier/S1462399425000122/type/journal_article
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AT dejiangpang retinoicacidinduced1geneandneuropsychiatricdiseasesasystematicreview
AT chunyuli retinoicacidinduced1geneandneuropsychiatricdiseasesasystematicreview
AT huifangshang retinoicacidinduced1geneandneuropsychiatricdiseasesasystematicreview