Background: We describe a four-generation Italian family with familial hemiplegic migraine (FHM) and epilepsy due to a novel ATP1A2 missense mutation (R1007W).
Case Results: Mutational analysis revealed a heterozygous nucleotide substitution c.3019C>T resulting in the missense substitution p.Arg1007Trp (p.R1007W) in seven subjects: Three individuals had hemiplegic migraine, two exhibited a clinical overlap between migraine and epilepsy, one had migraine and one was unaffected. The identified ATP1A2 mutation was not found in an ethnically matched control population of 190 individuals and was not reported in a polymorphisms database. In two-electrode voltage-clamp experiments on XENOPUS oocytes, the ATP1A2 R1007W mutant showed (i) reduced ion pumping activity due to a more profound voltage dependence and (ii) decreased apparent affinity for extracellular K⁺ at voltages around the cellular resting potential. This distinct type of loss of function has not been reported for other FHM2 mutations and can lead to impaired K⁺ clearance and elevated K⁺ levels in the CNS.
Conclusions: The functional data and clinical evidence suggest that in FHM2 migraine and epilepsy may originate from the same pathogenic mechanisms associated with genetically determined alterations of ion channels and pumps. Our data also support the hypothesis that the new mutation R1007W in our family may be a susceptibility factor for epilepsy.
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http://dx.doi.org/10.1177/0333102413495116 | DOI Listing |
Brain Commun
December 2024
Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
Familial hemiplegic migraine type 2 results from pathogenic variants in the gene, which encodes for a catalytic subunit of sodium/potassium ATPase. This extremely rare autosomal dominant disorder manifests with a spectrum of symptoms, most commonly pure hemiplegic phenotype, epilepsy, and/or intellectual disability. In this study, we detail the clinical features and genetic analysis of nine patients from a large family spanning four generations, with all carrying a previously unreported likely pathogenic variant, p.
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December 2024
Cao County People's Hospital, Heze, The People's Republic of China.
Contraception
December 2024
Department of Obstetrics, Gynecology & Women's Health, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, United States.
We present a case of suspected induced intractable headaches and paralysis after receiving an etonogestrel 68 mg implant. After extensive neurological evaluation, the etonogestrel implant was removed and neurological symptoms resolved. The case raises concerns about a potential rare risk of progestin-containing contraceptives in patients with migraines with aura warranting further investigation.
View Article and Find Full Text PDFNeuropediatrics
December 2024
GIGA - Cyclotron Research Center (CRC) - Rare Movement Disorders Research Group, University of Liège, Liège, Belgium.
and genes encode proteins forming transmembrane channels, Na/K/ATPase transporter, and voltage-gated calcium channels, respectively. Pathogenic variants in these genes are associated with hemiplegic migraines, movement disorders, and developmental and epileptic encephalopathy.We report a child presenting epileptic encephalopathy with cognitive and behavioral troubles.
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