title: First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia.
abstract: Neonatal hypotonia is frequently observed with a highly variable clinical presentation. Congenital myopathies that are classically characterized by the presence of structural changes of the muscle fibres such as cores, rods and aggregates have been reported to be occasionally associated with this presentation. However, the identification of the causing defect can be a challenging task in severe neonatal forms of the disease since specific structural changes might not always be present in affected newborn's muscles. The RYR1 gene encodes the skeletal muscle isoform of a calcium channel, the ryanodine receptor, and has been involved in both dominant and recessive congenital myopathies associated with structural changes and presenting with various degree of severity. Here we report the case of a child presenting at birth with a lethal form of neonatal hypotonia associated with an atypical congenital myopathy. Molecular investigations showed that the disease was caused by two novel RYR1 mutations. One of the mutations was a large-sized genomic deletion. This is the first genomic rearrangement identified into the RYR1 gene to our knowledge. This new class of mutation of the RYR1 gene will clearly have consequences for the molecular investigation of RYR1-related diseases.
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire, CHU de Grenoble, Grenoble, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marty
authors.forename: Yves
authors.initials: Y
authors.lastname: Nivoche
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
mesh_terms: D015153:Blotting, Western; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D009123:Muscle Hypotonia / Q000235:genetics* / Q000473:pathology; D009132:Muscles / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel