A second locus for autosomal dominant myopathy with proximal muscle weakness and early respiratory muscle involvement: a likely chromosomal locus on 2q21
Introduction
In 1990, L. Edström et al. described the clinical picture of 16 patients from seven families exhibiting an autosomal dominant, adult onset myopathy with early respiratory muscle weakness [1]. Recently, the disorder was mapped to chromosome 2q24-31 by our group [2]. In 1989, Chapon et al. reported on a French family exhibiting an autosomal dominant myopathy and respiratory insufficiency as the prominent disability [3]. There are close similarities (clinical and pathological) between the French myopathy and the Swedish one described, such as later onset, dominant inheritance, proximal muscle weakness, early respiratory muscle involvement, normal (or slightly elevated) serum CK and numerous myofibrillar lesions or so-called cytoplasmic bodies in muscle biopsy, which were strongly stained with rhodamine-conjugated phalloidin (Table 1).
Since the Swedish myopathy was found to be linked to chromosome region 2q24-q31, the French family was referred to us for linkage analysis of the same region; however, region 2q24-31 was completely excluded by haplotype analysis. In order to localise the disease gene for the French family, a genome-wide screening was performed using the Human Genome Screening kit (version 6.0).
Section snippets
Materials and methods
Three generations of a French family (five affected and six normal individuals) suffering from a familial cytoplasmic body myopathy were investigated. Clinical and pathological features of these individuals have been reported in detail elsewhere [3], [4], [5]. The affected individuals were characterised by proximal muscle weakness and early respiratory muscle involvement. The age of onset varied from 18 to 40 years. Muscle serum enzymes were within normal ranges, as was leukocyte acid maltase
Results
Clinically, the French family with early respiratory failure was considered to have the same disorder that the Swedish families had, which recently has been mapped to chromosome 2q24-q31. We thought that screening of the same region for the French family would confirm the linkage and probably narrow down the candidate region; therefore, 12 markers from densely mapped region of 2q24-q31 were tested for linkage. The markers covered the whole mapped region from D2S2363 to D2S2978 at intervals of
Discussion
Affected individuals in both families exhibit symptoms similar to those of limb-girdle muscular dystrophy (LGMD). LGMD is a clinically and genetically heterogeneous group of myogenic disorders with weakness beginning in the hip and shoulder girdle and later progressing to the distal muscles. Autosomal recessive (LGMD2) [12], [13] and dominant (LGMD1) [14], [15] inheritance patterns have been reported. Chromosomal loci have been localised for most of the autosomal recessive forms, LGMD2A, 2B,
Acknowledgements
This work is supported by grants from the Swedish Medical Research Council (No 3875), the Torsten and Ragnar Söderberg Foundation, the Petrus and Augusta Hedlunds Foundation. We wish to thank Dr Fangyuan Li for helping with the simulation analysis, Dr Jill Thyboll for collecting the samples and Ann-Christin Thelander for technical assistance.
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Differential Isoform Expression and Selective Muscle Involvement in Muscular Dystrophies
2015, American Journal of PathologyAn Italian case of hereditary myopathy with early respiratory failure (HMERF) not associated with the titin kinase domain R279W mutation
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Protein Aggregate Myopathies
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