Heterozygous microdeletions of 15q13.3 encompassing the candidate gene CHRNA7 are associated with developmental delay or intellectual disability with speech problems, hypotonia, and seizures.
Although deletions of CHRNA7 have been associated with intellectual disability (ID), seizures and neuropsychiatric phenotypes, the pathogenicity of CHRNA7 duplications has been uncertain.
Absence of the Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) gene product is proposed as a possible mechanism for the severe visual impairment; absence of CHRNA7 (alpha7-nicotinic receptor subunit) as a cause of the refractory seizures and severe cognitive impairment; and deletion of MTMR10 and/or MTMR15 (encoding myotubularin related proteins) alone or combined with other homozygously deleted genes as a cause for the congenital hypotonia with areflexia.
Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures.
Sensitivity to the seizure-inducing effects of nicotine is associated with strain-specific variants of the alpha 5 and alpha 7 nicotinic receptor subunit genes.