Figure 1
From: Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable
Inheritance pattern of the M1627K mutation in DIV/S4–5 linker in Na v 1.7 in familial PEPD. A, Inheritance of PEPD in two generations of a family with PEPD from the UK. Circles denote females; squares denote males, and symbols with diagonal line denote deceased individuals. The proband is indicated by an arrow. Blackened symbols indicate subjects affected with PEPD. B, Sequence traces of a segment of exon 26 in the region which encodes M1627. Left trace shows homozygous T4879 from exon 26 of the unaffected brother of the proband. Right trace shows heterozygous T4879A in exon 26 from the proband. This missense mutation leads to M1627K substitution. In (A), a (+) symbol denotes subjects heterozygous for the T4879A mutation in exon 26, and a (-) symbol denotes subjects without the mutation. Inheritance of PEPD segregates with the T4879A heterozygosity. C, Sequence alignment of DIV/S4–S5 linker from human sodium channels. The M1627K substitution in this family with PEPD is noted in the sequence from Nav1.7. The M1476I from a family with cold-induced myotonia occurs at the corresponding site as M1627 in Nav1.4. The M1652R from a family with LQT-3 occurs at the adjacent methionine residue in Nav1.5 (M1628 in Nav1.7).