A novel CLCN1 mutation: P480T in a Japanese family with Thomsen's myotonia congenita.

At least 50 disease-causing mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1), almost all of which originate from Caucasian families, have been identified. We investigated a Japanese family with Thomsen's myotonia congenita that included 16 affected individuals (8 men and 8 women) through five generations. Polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) screening of 11 members showed an aberrant conformer in exon 13 of CLCN1 complementary DNA (cDNA) in 8 affected and 1 unaffected members. By sequence analysis, we identified a C-to-A transition at nucleotide position 1438, resulting in a substitution of proline for threonine at amino acid position 480 (P480T), the same position of the original mutation (P480L) in Thomsen's disease. The P480T mutation was novel and absent in 100 normal controls. Seven of the 8 affected individuals were heterozygous; another, from affected parents, was homozygous. Clinically, myotonia in the homozygous patient was more severe than that in heterozygous patients, probably due to the gene dosage effect. On a long-train nerve-stimulation test at a rate of 3 Hz, M-wave responses in the homozygous patient showed marked decrement followed by recovery. In contrast, the heterozygous patients showed just a slight decrement or no changes, and none of 2 patients with myotonic muscular dystrophy or 2 normal controls revealed any decrement. Thus, the long-train nerve-stimulation test at a low stimulus frequency may be a useful tool to assess the disease-severity/genotype relationship in myotonia congenita.

[Rendu-Osler-Weber syndrome presented paramedian thalamic and midbrain infarcts and primary medullary hemorrhage: a case report].

We reported a 41-year-old male with paramedian thalamic and midbrain infarcts due to cerebral embolism from bilateral pulmonary arterio-venous fistula and primary medullary hemorrhage. The patient had an episode of sudden onset consciousness disturbance with left Weber's syndrome (right hemiplegia and left oculomotor palsy) and vertical gaze palsy at age of 23. He noticed numbness in the left hand and the left half body under clavicular when he had got up in a morning at age 41. He had headache and left tinnitus on second and third days, and on the 3rd and 4th days, he experienced nausea. He had severe hiccup persisting from the 6th to the 13th days. The 23rd days he was admitted to our hospital. He showed dysesthesia and paresthesia in left half body under clavicular, dysesthesia in left hand and vertical gaze palsy and convergence disturbance. MRI performed on the 18th and 24th days, disclosed hyperdense mass in T1 and T2-weighted images in dorsal site of medulla, but the 70th days MRI showed no abnormal lesions. Therefore we diagnosed the high intensity mass as primary medullary hemorrhage. Cerebral angiography showed no abnormal vasculature. Many members of his family had history of sever nasal bleeding. He had skin hemangioma and mucosal hemangioma in esophagus, stomach, colon and rectum, and bilateral pulmonary arterio-venous fistula which had been operated at age 39. His mother also had skin hemangioma and pulmonary arterio-venous fistula. Therefore this family was diagnosed Rendu-Osler-Weber syndrome (hereditary hemorrhagic telangiectasia). MRI also disclosed multiple cerebral infarctions in bilateral thalamus, left cerebral peduncle and left cerebellar hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)