FIGURE 1:

Identification of two novel missense mutations in MYBPC1 underlying the development of skeletal myopathy with tremor. (A) Schematic representation of the structure of sMyBP-C. Dark and light gray horizontal lines correspond to the Pro/Ala–rich region and the M-motif, respectively, whereas vertical colored lines in the NH₂ terminus, domain C7, and the extreme COOH terminus represent alternatively spliced segments. Green and blue rectangles denote immunoglobulin (Ig) and fibronectin-III (Fn-III) domains, respectively. The two novel MYBPC1 human mutations, Y247H and E248K, and their location in the sMyBP-C M-motif are indicated. (B) Pedigree of family 1 and sequence chromatograms showing the c.742G>A, p.(E248K) mutation in affected individuals II-3, III-3, and III-5 after exome sequencing and the wild-type sequence in the II-2 unaffected individual. (C) Pedigree of family 2 and sequencing chromatograms showing the c.739T>C, p.(Y247H) mutation in affected individuals III-2, IV-1, and V-1 and wild-type sequence at this position in an unaffected individual (II-3). For both pedigrees, black and white symbols indicate affected and unaffected individuals, respectively, whereas index patients are denoted with arrows.