Authors
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, Angela Lee, Randi N Gadea, Berten Ceulemans, Peter A M de Witte, Daniëlle Copmans, Anna C Jansen, R Frank Kooy
Published in
European journal of human genetics : EJHG. Jul 01, 2026. Epub Jul 01, 2026.
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.
PMID:
42386996
Bibliographic data and abstract were imported from PubMed on 02 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 7
- Comments 0