PMC:2725236 / 19137-20967 JSONTXT

{"project":"2_test","denotations":[{"id":"19646677-17140658-2044588","span":{"begin":528,"end":530},"obj":"17140658"},{"id":"19646677-17944572-2044589","span":{"begin":679,"end":681},"obj":"17944572"},{"id":"19646677-12602514-2044590","span":{"begin":813,"end":815},"obj":"12602514"},{"id":"19646677-15128042-2044591","span":{"begin":917,"end":919},"obj":"15128042"},{"id":"19646677-19019440-2044592","span":{"begin":965,"end":967},"obj":"19019440"},{"id":"19646677-15128042-2044593","span":{"begin":1113,"end":1115},"obj":"15128042"},{"id":"19646677-16997282-2044594","span":{"begin":1336,"end":1338},"obj":"16997282"}],"text":"In summary, we have used a positional fine-mapping approach to demonstrate association between ATP2C2 and CMIP and nonword repetition performance across two independent language-impaired populations. We propose that variants in both loci combine to modulate nonword-repetition performance in language-impaired populations. Both genes are expressed in the brain and represent good candidates for language- and memory-related processes. ATP2C2 is involved in the translocation of cytosolic calcium and manganese ions to the golgi.22 Calcium homeostasis is important for the regulation of many neuronal processes, including working memory, synaptic plasticity, and neuronal motility38, and manganese dysregulation has been linked to Parkinsonism (MIM #168600), Alzheimer disease (MIM #104300), and disordered memory.39 The functional role of CMIP is less defined, but it is known to interact with filamin A (MIM #300017)40 and the NF-kappaB subunit RelA (MIM #164014).41 The filaminA protein is involved in the reorganization of the actin cytoskeleton, which is of importance in the formation of the dendritic spine.40 The NF-κB family of transcription factors plays a central role in many neuronal processes, including synaptic activity and memory formation, and members of this family have been implicated in neurodegenerative disorders.42 Further characterization of the observed associations has enabled us to infer that SLI represents a qualitatively distinct disorder caused by a combination of genetic variants that disrupt multiple pathways important to the development of language. It is anticipated that the functional characterization of ATP2C2 and CMIP will promote a better understanding of the molecular basis of language acquisition and aid in the diagnosis and treatment of individuals affected by language disorders."}