{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:57:57Z","timestamp":1761101877713,"version":"build-2065373602"},"reference-count":22,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>To identify pathogenic mutant alleles of the <jats:italic>PYGM<\/jats:italic> gene in \u201cgenetic manifesting heterozygous\u201d patients with McArdle disease\u2014that is, those in whom we could only find a sole mutant allele by genomic DNA analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>We studied four unrelated patients. PCR-RFLP, gene sequencing, and muscle cDNA analysis were performed to search for mutations in the <jats:italic>PYGM<\/jats:italic> gene. The effects of the mutations were evaluated by in silico analysis, and gene expression was assessed by real-time polymerase chain reaction (PCR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Patient 1 was a compound heterozygous for the p.G205S missense mutation and for a novel \u201cin frame\u201d mutation, p.Q176_M177insVQ, resulting from a retention of six nucleotides from the 3\u2032-end sequence of intron 4. Patient 2 was heterozygous for the common nonsense mutation p.R50X, and for a 1094 bp, c.1969+214_2177+369del mutation, spanning from intron 16 to intron 17 sequences. Furthermore, mRNA expression level was dramatically reduced consistent with nonsense mediated decay. Patient 3 was heterozygous for the p.R50X substitution, and patient 4 was heterozygous for the relatively common private Spanish mutation p.W798R. These two patients harboured a heterozygous exonic synonymous variant, p.K215K. Quantification of gene transcripts in patient 3 revealed a drastic decrease in the relative expression of the gene, which strongly supports the possibility of nonsense mediated decay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Our results indicate that skeletal muscle cDNA studies in \u201cgenetic manifesting heterozygous\u201d patients with McArdle disease are prone to identify their second mutant allele.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.059469","type":"journal-article","created":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T13:49:01Z","timestamp":1235742541000},"page":"198-202","source":"Crossref","is-referenced-by-count":15,"title":["Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA"],"prefix":"10.1136","volume":"46","author":[{"given":"I","family":"Garc\u00eda-Consuegra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J C","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Nogales-Gadea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Bautista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Cabello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Luc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A L","family":"Andreu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Arenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2009,2,27]]},"reference":[{"key":"2025101711094952000_46.3.198.1","unstructured":"Dimauro S Tsujino S . Non-lysosomal glycogenoses. In: Engel A G , ed. Myology. 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Molecular heterogeneity of myophosphorylase deficiency (McArdle\u00e2\u0080\u0099s disease): a genotype-phenotype correlation study. Ann Neurol 200;50:574\u00e2\u0080\u009381.","DOI":"10.1002\/ana.1225.abs"},{"key":"2025101711094952000_46.3.198.8","unstructured":"Arenas J Martin MA Andreu AL . Glycogen storage disease type V. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Seattle: University of Washington, 1997\u00e2\u0080\u00932006. http:\/\/www.genetests.org . 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