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. 2022 Aug 26;10:944784. doi: 10.3389/fped.2022.944784

Figure 1.

Figure 1

(A) Time-line and family tree. Each parent is asymptomatic and a carrier for one variant. (B) Scheme of the pore forming alpha subunit of NaV1.4 with locations of CMS/myopathy-linked SCN4A variants: red p.(N1205K) and p.(R1454W) (compound heterozygous), gray (other previously reported variants): p.R104H, p.R225W, p.S246L, p.Q470X, p.A1049VfsX50, p.D1059N, p.R1059X, p.R1135C, p.C1205F, p.V1442Q, p.R1457H p.R1460W/Q, p.H1782QfsX85. (C) Amino acid conservation in the extracellular S5-S6 reentrant loop region of domain III among NaV1.4 homologs. The variant SCN4A:p.N1205K affects a highly conserved amino acid in NaV1.4 both in orthologs (top) and human paralogs (bottom). Variants paralogous to p.(N1205K) (marked in red) in NaV1.1 (SCN1A:p.(N1392K), twice), NaV1.5 (SCN5A:p.(N1380K), thrice) and NaV1.8 (SCN10A:p.(N1328K), once) were reported in patients with neurological or cardiac phenotypes and electrophysiological evaluation in NaV1.5 supported a loss-of-function effect.