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A splice-site mutation causing ovine McArdle's disease
Journal article   Peer reviewed

A splice-site mutation causing ovine McArdle's disease

P. Tan, J.G. Allen, S.D. Wilton, P.A. Akkari, C.R. Huxtable and N.G. Laing
Neuromuscular Disorders, Vol.7(5), pp.336-342
1997
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Abstract

McArdle's disease is an autosomal recessive myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme muscle glycogen phosphorylase which releases glucose for contraction during exercise. The human cDNA has been sequenced and disease-causing mutations identified. An ovine equivalent of McArdle's disease has been diagnosed and the mutation responsible identified by PCR-amplification of the ovine glycogen myophosphorylase cDNA in six overlapping fragments followed by single strand conformation polymorphism (SSCP) analysis. Two fragments showed SSCPs in the glycogen myophosphorylase cDNA from affected sheep. The SSCP in fragment one was a silent polymorphism, while that in fragment six, was an eight base deletion at the 5′ end of exon 20. This deletion will cause a frame-shift, a premature stop codon and remove the last 31 amino-acid residues from the protein. The cDNA deletion suggested that the genomic mutation most likely involved a splice-site. Sequencing intron 19 identified the mutation as an adenine for guanine substitution at the intron 19 3′ splice-site. This eliminated an XbaI site present in normal sheep allowing diagnosis of normal, affected and carrier sheep. This ovine model of McArdle's disease is now available for therapeutic trials.

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Collaboration types
Domestic collaboration
Citation topics
1 Clinical & Life Sciences
1.271 Lysosomal Storage Disorders
1.271.2265 Glycogen Storage Diseases
Web Of Science research areas
Clinical Neurology
Neurosciences
ESI research areas
Neuroscience & Behavior
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