Figure 1.

Phenotypic and genetic characteristics of CMT2C. a) Marked variability of disease severity is demonstrated by mild, late onset weakness in subject F1.III.2, but severe quadriparesis and respiratory failure in her daughter, subject F1.IV.4. Written consent was obtained to publish these photographs. b) Light microscope images of hematoxylin and eosin-stained sections of gastrocnemius muscle biopsy from subject F1.IV.4 demonstrating profound denervation atrophy of muscle. Scale bar=10 µm. c) Toluidine blue-stained section of sural nerve shows mild loss of large, sensory myelinated axons. Scale bar=10 µm. d) Electron microscopy of sural nerve confirms mild loss of large and small myelinated axons and unmyelinated axons. Scale bar=10µm. e) Arrow demonstrates a rare axon undergoing Wallerian-like axonal degeneration. Scale bar=2µm. f) Pedigrees of Families 1 and 2 demonstrating affected subjects in each of 3 generations. White=unaffected, black=affected, and grey=unknown disease status. *Sample collected. g) The haplotypes for subjects F1.V.3 and F2.IV.12 are demonstrated. Family 1 defines the lower border (marker D12S1343) and Family 2 defines the upper border (marker D12S105) of the region of interest. The bracket indicates the linked region. h) Sequencing shows a heterozygous C>T change at position 805 in Family 1 and a G>A change at position 806 in Family 2 in the TRPV4 gene. i) Protein homology of TRPV4 in various species. The mutations result in amino acid substitutions at R269, a highly conserved residue.