Two novel functional mutations in the Na+,K+-ATPase alpha 2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Castro, MJ (Author) Other; Nunes, B (Author) Other; de Vries, B (Author) Other; Carolina Lemos (Author) Other; Vanmolkot, KRJ (Author) Other; van den Heuvel, JJMW (Author) Other; Temudo, T (Author) Other; Barros, J (Author) Other; Sequeiros, J (Author) ICBAS; Frants, RR (Author) Other; Koenderink, JB (Author) Other; Jose Pereira Monteiro (Author) ICBAS; van den Maagdenberg, AMJM (Author) Other

Journal

Title: Clinical Genetics

Vol. 73

Pages: 37-43

ISSN: 0009-9163

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-004-2TD

DOI: 10.1111/j.1399-0004.2007.00918.x

Abstract (EN): Mutations in the ATP1A2 gene, encoding the alpha 2-subunit of the Na+,K+-ATPase, are associated with familial hemiplegic migraine type 2. The majority of ATP1A2 mutations were reported in patients with hemiplegic migraine without any additional neurological findings. Here, we report on two novel ATP1A2 mutations that were identified in two Portuguese probands with hemiplegic migraine and interesting additional clinical features. The proband's of family 1 (with a V362E mutation) had mood alterations, classified as a borderline personality. The proband in family 2 (with a P796S mutation) had mild mental impairment, in addition to hemiplegic migraine; more severe mental retardation was observed in his brother, who also had hemiplegic migraine and carried the same mutation. Cell-survival assays clearly showed abnormal functioning of mutant Na+,K+-ATPase, indicating that both ATP1A2 mutants are disease causing. Additionally, our results suggest a possible causal relationship of the ATP1A2 mutations with the complex clinical phenotypes observed in the probands.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7