Titre :
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Anoctaminopathy in german patients with limb girdle muscular dystrophy and distal myopathy showing asymmetrical muscle involvement
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contenu dans :
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Auteurs :
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4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) ;
Joshi P ;
Glaser D ;
Hanisch F ;
Stoltenburg G ;
Zierz S ;
Deschauer M
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Type de document :
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Article
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Editeur :
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AFM-TELETHON, 2011
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Pages :
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p. 112
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Langues:
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Anglais
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Résumé :
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Recessive mutations in the Anoctamin 5 (ANO5) gene have been recently identified in families with limb girdle muscular dystrophy (LGMD2L) and distal myopathy type Miyoshi. Molecular genetic testing is necessary to detect patients with anoctaminopathy since testing on protein level (immunoblotting or immunohistochemistry of muscle) is not yet available. Anoctamin 5 is a putative calcium-activated chloride channel. Muscular pathology might be due defective membrane repair of sarcolemma. We screened German patients with autosomal recessive LGMD (n=6) and distal myopathy type Miyoshi (n=3) of unknown origin for c.191dupA (exon 5), c.1295C>G (exon 13), and p.R758C (exon 20) mutations in the ANO5 gene by PCR and direct sequencing. In all patients muscle biopsy revealed dystrophic or myopathic changes. Three patients with LGMD were positive for the c.191dupA mutation; two of them were homozygous and the other one heterozygous. Sequencing of all exons in the ANO5 gene is ongoing to detect the second mutation in the heterozygote patient. One patient with distal myopathy was compound heterozygous for the c.191dupA mutation and p.R758C mutation. Age of onset was 40, 48 and 64 years in patients with LGMD and 23 years in the patient with distal myopathy. There was remarkable asymmetric involvement in all four patients. CK levels were elevated 13-30 times. EMG investigations showed myopathic changes without myotonic discharges. In conclusion, Anoctaminopathy might be rather common in German patients with LGMD and distal myopathy type Miyoshi. Very late onset is possible and asymmetric presentation seems to be characteristic for an anoctaminopathy.
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