CMIP(c-maf inducing protein), located on chromosome 16q23.2, encodes a multi-domain adaptor protein comprising an N-terminal pleckstrin homology domain, a central region enriched in protein–protein interaction motifs, and a C-terminal leucine-rich repeat domain. Genome-wide association studies (GWAS) have implicated CMIPin specific language impairment, reading ability, and general cognitive performance. Clinically, CMIP-related disorders are associated with a broad neurodevelopmental and neuropsychiatric phenotype, characterized by a high prevalence of developmental delay, autism spectrum disorder traits, attention-deficit/hyperactivity disorder features, and additional psychiatric comorbidities. Epilepsy occurs in a subset of affected individuals, although therapy-resistant seizures appear to be relatively uncommon.
To further investigate the pathogenicity of CMIPvariants, a cmip mutant zebrafish model carrying a premature stop codon was generated and characterized. Mutant zebrafish displayed abnormal locomotor activity suggestive of seizure-like behavior, which was further supported by the presence of spontaneous epileptiform discharges in heterozygous mutant larvae. Together, the clinical findings and zebrafish data establish CMIPas a gene implicated in neurodevelopmental and neuropsychiatric disorders.
CMIP