Journal Article

Myotilin, a Novel Sarcomeric Protein with Two Ig-like Domains, is Encoded by a Candidate Gene for Limb-Girdle Muscular Dystrophy

Paula Salmikangas, Olli-Matti Mykkänen, Mikaela Grönholm, Leena Heiska, Juha Kere and Olli Carpén

in Human Molecular Genetics

Volume 8, issue 7, pages 1329-1336
Published in print July 1999 | ISSN: 0964-6906
Published online July 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.7.1329
Myotilin, a Novel Sarcomeric Protein with Two Ig-like Domains, is Encoded by a Candidate Gene for Limb-Girdle Muscular Dystrophy

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The striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin, a giant molecule that contains several immunoglob-ulin (Ig)-like domains and associates with thin and thick filaments, and α-actinin, an actin cross-linking protein. Mutations in several sarcomeric and sarco-lemmal proteins have been shown to result in muscular dystrophy and cardiomyopathy. On the other hand, the disease genes underlying several disease forms remain to be identified. Here we describe a novel 57 kDa cytoskeletal protein, myotilin. Its N-terminal sequence is unique, but the C-terminal half contains two Ig-like domains homologous to titin. Myotilin is expressed in skeletal and cardiac muscle, it co-localizes with α-actinin in the sarcomeric I-bands and directly interacts with α-actinin. The human myotilin gene maps to chromosome 5q31 between markers AFM350yB1 and D5S500. The locus of a dominantly inherited limb-girdle muscular dystrophy (LGMD1A) resides in an overlapping narrow segment, and a new type of distal myopathy with vocal cord and pharyngeal weakness (VCPMD) has been mapped to the same locus. The muscle specificity and apparent role as a sarcomeric structural protein raise the possibility that defects in the myotilin gene may cause muscular dystrophy.

Journal Article.  5364 words.  Illustrated.

Subjects: Genetics and Genomics

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