Molecular Diagnosis of Hereditary Myotonic Disorders
Date Issued
2012
Date
2012
Author(s)
Tsai, Hui-Szu
Abstract
Myotonia is the delayed relaxation of skeletal muscle after voluntary contraction which might cause trouble in daily life. Myotonic disorders include the myotonic dys-trophies and nondystrophic myotonias (NDM). Mutations in the genes encoding chlo-ride (CLCN1) or sodium (SCN4A) channels result in muscle fiber hyperexcitability in patients with NDM. The phenotype of NDM is variable leading to difficulties in clinical diagnosis. The aim of the study is to identify the mutations in the two responsible genes from patients with NDM and to correlate the clinical phenotypes and genotypes.
We have 12 volunteers from 7 Taiwanese families with the problem of NDM. Mu-tation screening identified 2 families with CLCN1 mutations and 5 with SCN4A muta-tions. Clinically, patients with CLCN1 mutations (L198R and A402V) demonstrated marked myotonia with hypertrophic muscles. The age of onset of the patients is early at the first decade. Five index patients harbor four individual SCN4A mutations (V445M, V781I, T1313M and A1737T) with variable clinical features such as potassi-um-aggravated myotonia, paramyotonia congenita, or hyperkalemic-periodic paralysis. The age of onset is also quite young, at 1st ~2nd decades of life. Two mutations, L198R in CLCN1 and A1737T in SCN4A genes are novel. In our experience, it seems that fre-quency of a SCN4A mutation is higher than that of the CLCN1 mutation in Taiwanese patients with NDM. Herein, the details of the phenotypes of each mutant genotype have been discussed.
Subjects
Myotonic disorder
sodium channel
chloride channel
SCN4A gene
CLCN-1 gene
Type
thesis
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