CMIP as a novel candidate gene for neurodevelopmental and neuropsychiatric disorders.

Creator(s)

• Matthias De Wachter
• Mathijs B. van der Lei
• Amber Decleve
• Kevin De Man
• Ellen Elinck
• An-Sofie Schoonjans
• Evan Gouy
• Louis Januel
• Pauline Monin
• Audrey Labalme
• Amelle Shillington
• Himanshu Goel
• Juliet P. Taylor
• Katherine Neas
• David A. Koolen
• Francois Lecoquierre
• Alice Goldenberg
• Theresa Brunet
• Melanie Brugger
• Minjie Luo
• Magdalena Krygier
• Maria Mazurkiewicz-Bełdzińska
• Manon Degoutin
• Claire Beneteau
• Cyril Goizet
• David D. Weaver
• Emily G. Farrow, Children's Mercy HospitalFollow
• Angela Lee, Children's Mercy Kansas CityFollow
• Randi N. Gadea, Children's Mercy Kansas CityFollow
• Berten Ceulemans
• Peter A M de Witte
• Daniëlle Copmans
• Anna C. Jansen
• R Frank Kooy

Document Type

Article

Publication Date

8-2026

Identifier

DOI: 10.1038/s41431-026-02169-9; PMCID: PMC13424592

Abstract

CMIP, a c-maf inducing protein that plays a key role in cytoskeletal remodeling, neuronal migration and synaptic formation, was first associated with specific language impairment and autism through the identification of a deletion in a single patient in 2012. Since then, only two additional individuals with CMIP deletions have been reported, both sharing features of autism and gastrointestinal features. However, a firm causal relationship between variants in CMIP and neurodevelopmental disorders has not yet been established. In this multicentre cohort study, we identified 25 individuals, from 17 unrelated families, with CMIP-related neurodevelopmental disorders, 22 of whom have not been previously reported. Of these, seven individuals carried heterozygous loss-of-function CMIP single-nucleotide variants, while the other 18 individuals had a complete or partial deletion of CMIP, some involving adjacent genes. The clinical phenotype was variable with a high prevalence of developmental delay (20/25), autism spectrum disorder features (13/25), attention-deficit/hyperactivity disorder features (11/25) and other psychiatric disorders (15/25). Epilepsy was present in nine individuals (9/25), of whom three had therapy-resistant seizures. To study the pathogenicity of CMIP variants, a cmip mutant zebrafish model carrying a premature stop codon was investigated. These mutants showed temperature-dependent altered locomotor activity suggestive of seizure-like behavior, which was confirmed by spontaneous epileptiform discharges in cmip^+/- mutant zebrafish larvae. Our patient cohort and the zebrafish data establish CMIP as a gene implicated in neurodevelopmental and neuropsychiatric disorders. We recommend inclusion of CMIP in the genetic work-up of neurodevelopmental delay, with or without autism or psychiatric disorders and epilepsy.

Journal Title

European journal of human genetics : EJHG

Volume

34

Issue

8

First Page

1070

Last Page

1080

MeSH Keywords

Humans; Cohort Studies; Adaptor Proteins, Signal Transducing; Animals; Zebrafish; Retrospective Studies; Male; Female; Infant; Child, Preschool; Child; Adolescent; Adult; Middle Aged; Neurodevelopmental Disorders; Gene Deletion; DNA Copy Number Variations; Gastrointestinal Diseases; RNA, Messenger; Gene Expression; Disease Models, Animal; Zebrafish Proteins; Mental Disorders

PubMed ID

42386996

Keywords

Cohort Studies; Signal Transducing Adaptor Proteins; Zebrafish; Retrospective Studies; Neurodevelopmental Disorders; Gene Deletion; DNA Copy Number Variations; Gastrointestinal Diseases; Messenger RNA; Gene Expression; Animal Disease Models; Zebrafish Proteins; Mental Disorders

Recommended Citation

De Wachter M, van der Lei MB, Decleve A, et al. CMIP as a novel candidate gene for neurodevelopmental and neuropsychiatric disorders. Eur J Hum Genet. 2026;34(8):1070-1080. doi:10.1038/s41431-026-02169-9