IngentaConnect Two novel functional mutations in the Na,K-ATPase 2-subunit ATP1A...

Authors: Castro; Nunes¹; de Vries,²; Lemos; Vanmolkot²; van den Heuvel,³; Temudo⁴; Barros⁵; Sequeiros; Frants²; Koenderink³; Pereira-Monteiro; van den Maagdenberg,

Source: Clinical Genetics, Volume 73, Number 1, January 2008 , pp. 37-43(7)

Publisher: Blackwell Publishing

Abstract:

Castro M-J, Nunes B, de Vries B, Lemos C, Vanmolkot KRJ, van den Heuvel JJMW, Temudo T, Barros J, Sequeiros J, Frants RR, Koenderink JB, Pereira-Monteiro JM, van den Maagdenberg AMJM. Two novel functional mutations in the Na⁺,K⁺-ATPase α2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes.

Clin Genet 2008: 73: 37-43. © Blackwell Munksgaard, 2008

Mutations in the ATP1A2 gene, encoding the α2-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.

Keywords: borderline personality disturbance; cell survival; FHM2; mental retardation; migraine

Document Type: Original article

DOI: 10.1111/j.1399-0004.2007.00918.x

Affiliations: 1: Serviço de Neurologia, Hospital Pedro Hispano, Porto, Portugal 2: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands 3: Department of Pharmacology and Toxicology, University Medical Centre St Radboud, Nijmegen, the Netherlands 4: Serviço de Pediatria, Hospital Geral de Santo António, Porto, Portugal 5: Serviço de Neurologia, Hospital Geral de Santo António, Porto, Portugal

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.16 plus tax Refund Policy

Two novel functional mutations in the Na+,K+-ATPase α2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes

Two novel functional mutations in the Na⁺,K⁺-ATPase α2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes