Titre :
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Congenital myopathies caused by absence of skeletal muscle alpha actin (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Nowak K ;
Sewry C ;
Navarro C ;
Reina C ;
Muntoni F ;
Laing N
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 162
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Langues:
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Anglais
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Mots-clés :
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actine
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biologie moléculaire
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colloque
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consanguinité
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degré de sévérité
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Espagne
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gène ACTA1
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histopathologie
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microscopie électronique
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muscle squelettique
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mutation génétique
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nourrisson
;
Tsiganes
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Résumé :
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Communication n° 178. INTRODUCTION Dominant and recessive mutations have been identified in the skeletal muscle alpha actin gene (ACTA1). Previously, one child from a consanguineous French Gypsy kindred has been described who was homozygous for a nonsense mutation in ACTA1. That child had no voluntary movements at birth (1). OBJECTIVES To describe two further patients with homozygous ACTA1 null mutations. METHODS DNA samples from the patients were analysed by PCR and sequencing of the six ACTA1 coding exons. Western blots were performed with various antibodies. RESULTS Two infants from consanguineous kindreds were identified with different homozygous ACTA1 null mutations: a Spanish Gypsy (Tyr362fs) and a British patient of Pakistani origin (Asp179fs). The Spanish patient had no voluntary movements at birth. However the British patient has spontaneous respiration and some anti-gravity limb movements. He required naso-gastric tube feeding until 11 months followed by a gastrostomy. Since 16 months, he is non-invasively ventilated at night. Histopathology: British patient - type 1 hypotrophy and some core-like areas lacking oxidative enzyme stains. Electron microscopy revealed disrupted Z lines and some rod shaped structures. Spanish patient - severe architectural changes with fatty and connective tissue replacement and small muscle fibers. Fiber type differentiation was normal. Electron microscopy disclosed multiple small rods in most muscle fibers. Western blot analysis showed neither patient has skeletal muscle actin. Both patients have increased levels of cardiac actin in their skeletal muscles, with the British patient several times more than the Spanish. CONCLUSIONS The less severe disease in the British patient compared to the Spanish and French Gypsy patients may result from the greater levels of cardiac actin. REFERENCE 1. Romero NB, et al. (2003) Homozygous nonsense mutation of the ACTA1 gene - clinical phenotype and muscle pathology. Neuromuscular Disorders 13:619.
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