UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Graves TD, Rajakulendran S, Zuberi SM, Morris HR, Schorge S, Hanna MG, Kullmann DM
  • Publication date:
    27/07/2010
  • Pagination:
    367, 372
  • Journal:
    Neurology
  • Volume:
    75
  • Issue:
    4
  • Status:
    Published
  • Country:
    United States
  • PII:
    75/4/367
  • Language:
    eng
  • Keywords:
    Adult, Amino Acid Sequence, Ataxia, Child, Preschool, Epilepsy, Family Health, Female, Humans, Kv1.1 Potassium Channel, Male, Middle Aged, Molecular Sequence Data, Pedigree, Phenotype, Severity of Illness Index, Twins, Monozygotic, Videotape Recording, Young Adult
Abstract
OBJECTIVE: Episodic ataxia type 1 (EA1) is a monogenic channelopathy caused by mutations of the potassium channel gene KCNA1. Affected individuals carrying the same mutation can exhibit considerable variability in the severity of ataxia, neuromyotonia, and other associated features. We investigated the phenotypic heterogeneity of EA1 in 2 sets of identical twins to determine the contribution of environmental factors to disease severity. One of the mutations was also found in a distantly related family, providing evidence of the influence of genetic background on the EA1 phenotype. METHODS: We evaluated 3 families with an EA1 phenotype, 2 of which included monozygotic twins. We sequenced the KCNA1 gene and studied the biophysical consequences of the mutations in HEK cells. RESULTS: We identified a new KCNA1 mutation in each pair of twins. Both pairs reported striking differences in the clinical severity of symptoms. The F414S mutation identified in one set of twins also occurred in a distantly related family in which seizures complicated the EA1 phenotype. The other twins had an R307C mutation, the first EA1 mutation to affect an arginine residue in the voltage-sensor domain. Both mutants when expressed exerted a dominant-negative effect on wild-type channels. CONCLUSION: These results broaden the range of KCNA1 mutations and reveal an unexpectedly large contribution of nongenetic factors to phenotypic variability in EA1. The occurrence of epilepsy in 1 of 2 families with the F414S mutation suggests an interplay of KCNA1 with other genetic factors.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Department of Neuromuscular Diseases
Author
Clinical & Experimental Epilepsy
Author
Clinical and Movement Neurosciences
Author
UCL School of Pharmacy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by