Figure 1.
Sequence chromatography of the mutation and multiple sequence alignments for Nav1.4 channels. (A) The pedigrees from two individual families (Family I and II) with the index cases are shown in the upper and lower panels, respectively. Both index cases suffered from muscle myotonia with muscle hypertrophy. In Family I, the sister of the index case suffered from mental subnormality and one of her relative had seizure history. Both the index case and his brother from Family II suffered from myotonic myopathy. The sequence chromatography (left side of lower panel) shows a variant, c.G1333A at exon 9 of the SCN4A gene, which causes a p.V445M mutation. Both probands have the sequence variant. The variant is not found in the relatives of the index case of Family I. In Family II, both the proband and his brother share the same sequence variant. (B) The amino acid V445 is highly conserved among species during evolution and in the protein family of voltage-gated sodium channels. (C) The topology of the Nav1.4 channel shows that the mutation is located at the sixth transmembrane segment of Domain I (DI/S6).