title: Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts.
abstract: We report here the identification of a patient with muscle-specific glycogen synthase deficiency. The 8-year-old patient showed no prior signs of distress before collapsing during a bout of exercise, resulting in death. Initial post-mortem analysis of tissues suggested death was due to metabolic complications of mitochondrial myopathy, but upon further examination it was found that the anomalies were indicative of mitochondrial proliferation and oxidative compensation. A homozygous two base pair deletion was identified in exon 2 of GYS1, and the parents and sibling were confirmed as heterozygous carriers of the deletion. This case highlights the importance of differentiating between mitochondrial compensatory phenomena and true mitochondrial disease, and suggests that GYS1 deficiency could be a common cause of sudden cardiac death in children. Children with abnormal cardiac responses to increased workloads as well as those with defined myocardial disease should therefore be tested for GYS1 deficiency.
authors.affiliation: Genetics and Genome Biology, The Research Institute, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: Cameron
authors.forename: Valeriy
authors.initials: V
authors.lastname: Levandovskiy
authors.forename: Nevena
authors.initials: N
authors.lastname: MacKay
authors.forename: Rucha
authors.initials: R
authors.lastname: Utgikar
authors.forename: Cameron
authors.initials: C
authors.lastname: Ackerley
authors.forename: David
authors.initials: D
authors.lastname: Chiasson
authors.forename: William
authors.initials: W
authors.lastname: Halliday
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.forename: Brian H
authors.initials: BH
authors.lastname: Robinson
mesh_terms: D001483:Base Sequence; D002457:Cell Extracts; D002648:Child; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology*; D024982:Glycogen Phosphorylase, Muscle Form / Q000235:genetics*; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012867:Skin / Q000473:pathology*; D013010:Sonication; D013194:Staining and Labeling
chemical_list: D002457:Cell Extracts; D007773:Lactates; D024982:Glycogen Phosphorylase, Muscle Form