Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy

C Minetti, F Sotgia, C Bruno, P Scartezzini, P Broda… - Nature …, 1998 - nature.com
C Minetti, F Sotgia, C Bruno, P Scartezzini, P Broda, M Bado, E Masetti, M Mazzocco…
Nature genetics, 1998nature.com
Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group
of myopathies, including autosomal dominant and recessive forms1–3. To date, two
autosomal dominant forms have been recognized2, 3: LGMD1A, linked to chromosome 5q,
and LGMD1B, associated with cardiac defects and linked to chromosome 1q11–21. Here we
describe eight patients from two different families with a new form of autosomal dominant
LGMD, which we propose to call LGMD1C, associated with a severe deficiency of caveolin-3 …
Abstract
Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of myopathies, including autosomal dominant and recessive forms1–3. To date, two autosomal dominant forms have been recognized2,3: LGMD1A, linked to chromosome 5q, and LGMD1B, associated with cardiac defects and linked to chromosome 1q11–21. Here we describe eight patients from two different families with a new form of autosomal dominant LGMD, which we propose to call LGMD1C, associated with a severe deficiency of caveolin-3 in muscle fibres. Caveolin-3 (or M-caveolin) is the muscle-specific form of the caveolin protein family, which also includes cave-olin-1 and -2 (refs 4–9). Caveolins are the principal protein components of caveolae (50–100 nm invaginations found in most cell types) which represent appendages or sub-compartments of plasma membranes10,11. We localized the human caveolin-3 gene (CAV3) to chromosome 3p25 and identified two mutations in the gene: a missense mutation in the membrane-spanning region and a micro-deletion in the scaffolding domain. These mutations may interfere with caveolin-3 oligomerization and disrupt caveolae formation at the muscle cell plasma membrane.
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