Key result
In 354 cases with mutations in 7 channel-encoding genes, the most common phenotypes were intellectual disability (77.4%), seizures (69.8%), developmental delay (59.8%), and behavioral abnormalities (29.9%).
Why the study?
Ion channel dysfunction in the brain can impair neuronal membranes and lead to neurological diseases, especially neurodevelopmental disorders, requiring delineation of associated genotype and phenotype spectrums.
Observational (n=354)
Mutations in 7 channel-encoding genes are associated with a broad spectrum of neurological phenotypes, most commonly intellectual disability and seizures.
Background: Ion channel dysfunction in the brain can lead to impairment of neuronal membranes and generate several neurological diseases, especially neurodevelopmental disorders. Methods: In this study, we set out to delineate the genotype and phenotype spectrums of 14 Iranian patients from 7 families with intellectual disability (ID) and/or developmental delay (DD) in whom genetic mutations were identified by next-generation sequencing (NGS) in 7 channel-encoding genes: KCNJ10, KCNQ3, KCNK6, CACNA1C, CACNA1G, SCN8A, and GRIN2B. Moreover, the data of 340 previously fully reported ID and/or DD cases with a mutation in any of these seven genes were combined with our patients to clarify the genotype and phenotype spectrum in this group. Results: In total, the most common phenotypes in 354 cases with ID/DD in whom mutation in any of these 7 channel-encoding genes was identified were as follows: ID (77.4%), seizure (69.8%), DD (59.8%), behavioral abnormality (29.9%), hypotonia (21.7%), speech disorder (21.5%), gait disturbance (20.9%), and ataxia (20.3%). Electroencephalography abnormality (33.9%) was the major brain imaging abnormality. Conclusion: The results of this study broaden the molecular spectrum of channel pathogenic variants associated with different clinical presentations in individuals with ID and/or DD.
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Ehtesham et al. (2022) conducted an observational in Intellectual disability and/or developmental delay (n=354). Mutations in channel-encoding genes was evaluated on Phenotypic spectrum and frequency of clinical presentations. In 354 cases with mutations in 7 channel-encoding genes, the most common phenotypes were intellectual disability (77.4%), seizures (69.8%), developmental delay (59.8%), and behavioral abnormalities (29.9%).
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