Mental retardation affects 1–3% of the population and has a strong genetic etiology. Consequently, early identification of the genetic causes of mental retardation is of significant importance in the diagnosis of the disease, as predictor of the progress of the disease and for the determination of treatment. In this study, we identify mutations in the gene encoding for cyclin M2 (CNNM2) to be causative for mental retardation and seizures in patients with hypomagnesemia. Particularly, in patients with a recessive mode of inheritance, the intellectual disability caused by dysfunctional CNNM2 is dramatically severe and is accompanied by severely limited motor skills and brain malformations suggestive of impaired early brain development. Although hypomagnesemia has been associated to several neurological diseases, Mg2+ status is not regularly assessed in patients with seizures and mental disability. Our findings establish CNNM2 as an important protein for renal magnesium handling, brain development and neurological functioning, thus explaining the physiology of human disease caused by (dysfunctional) mutations in CNNM2. CNNM2 mutations should be taken into account in patients with seizures and mental disability, specifically in combination with hypomagnesemia.
Vyšlo v časopise: CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004267 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004267
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