P2.13 Proteolytic processing of C-terminal titin

Abstract

Mutations in the extreme C-terminal part of titin, residing in the sarcomeric M-band, lead to tibial muscular dystrophy (TMD), a dominant late-onset distal myopathy. In homozygotes, the same mutations cause the more severe recessive limb-girdle muscular dystrophy 2J (LGMD2J). The FINmaj mutation, underlying the titinopathies TMD/LGMD2J in Finnish patients, causes an exchange of four consecutive amino acids in the Ig-like domain M10, the most C-terminal domain of titin. Seven other missense or truncating mutations, all affecting M10 or the preceding is 7 region, are known to cause TMD/LGMD2J in other European populations.