{Reference Type}: Journal Article
{Title}: Clinical comparison and functional study of the L703P: a recurrent mutation in human SCN4A that causes sodium channel myotonia.
{Author}: Ke Q;Zhao Y;Li Y;Ye J;Tang S;He F;Ji F;Dai X;Ni J;Li Y;Griggs RC;Cheng X;
{Journal}: Neuromuscul Disord
{Volume}: 0
{Issue}: 0
{Year}: Aug 2022 17
{Factor}: 3.538
{DOI}: 10.1016/j.nmd.2022.08.004
{Abstract}: The non-dystrophic myotonias are inherited skeletal muscle disorders characterized by skeletal muscle stiffness after voluntary contraction, without muscle atrophy. Based on their clinical features, non-dystrophic myotonias are classified into myotonia congenita, paramyotonia congenita, and sodium channel myotonia. Using whole-exome next-generation sequencing, we identified a L703P mutation (c.2108T>C, p.L703P) in SCN4A in a Chinese family diagnosed with non-dystrophic myotonias. The clinical findings of patients in this family included muscle stiffness and hypertrophy. The biophysical properties of wildtype and mutant channels were investigated using whole-cell patch clamp. L703P causes both gain-of-function and loss-of-function changes in Nav1.4 properties, including decreased current density, impaired recovery, enhanced activation and slow inactivation. Our study demonstrates that L703P is a pathogenic variant for myotonia, and provides additional electrophysiological information for understanding the pathogenic mechanism of SCN4A-associated channelopathies.