Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVE: To evaluate clinical, genetic, and electrophysiologic features of patients with Andersen-Tawil syndrome (ATS) in the United Kingdom. METHODS: Clinical and neurophysiologic evaluation was conducted of 11 families suspected to have ATS. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control samples were screened by direct DNA sequencing. The electrophysiologic consequences of several new mutations were studied in an oocyte expression system. RESULTS: All 11 ATS families harbored pathogenic mutations in KCNJ2 with six mutations not previously reported. Some unusual clinical features including renal tubular defect, CNS involvement, and dental and phonation abnormalities were observed. Five mutations (T75M, D78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctional channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect. CONCLUSION: Six new disease-causing mutations in KCNJ2 were identified, one of which was in a PIP2 binding site. Molecular expression studies indicated that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important cause of ATS in the UK.

Original publication

DOI

10.1212/01.wnl.0000178888.03767.74

Type

Journal article

Journal

Neurology

Publication Date

11/10/2005

Volume

65

Pages

1083 - 1089

Keywords

Adolescent, Adult, Andersen Syndrome, Animals, Child, Child, Preschool, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Genetic Testing, Humans, Infant, Kidney Tubules, Male, Mutation, Oocytes, Phenotype, Potassium Channels, Potassium Channels, Inwardly Rectifying, Tooth Abnormalities, Xenopus laevis