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 reporte d. Some unusual clinical features including renal tubular defect, CNS involvemen t, and dental and phonation abnormalities were observed. Five mutations (T75M, D 78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctio nal channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect. Conclusion: Six new disease-causing m utations in KCNJ2 were identified, one of which was in a PIP2 binding site. Mole cular expression studies indicated that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important caus e of ATS in the UK. Objective: To evaluate clinical, genetic, and electrophysiologic features of patients with Andersen-Tawil syndrome (ATS) in the United Kingdom. Methods: Clinical and neurophysiologic evaluation were conducted on 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 e d. Some unusual clinical features including renal tubular defect, CNS involvemen t, and dental and phonation abnormalities were observed. Five mutations (T75M, D 78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctio nal channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect. Conclusion: Six new disease-causing m utations in KCNJ2 were identified, one of which was in PIP2 binding site. Mole cular expression studies indicate that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important caus e of ATS in the UK.