title: De novo RYR1 heterozygous mutation (I4898T) causing lethal core-rod myopathy in twins.
abstract: "Core-rod myopathy" is a rare congenital myopathy characterized by the presence of "cores" and "rods" in distinct locations in the same or different muscle fibres. This association is linked currently to mutations in RYR1, NEB and ACTA1 genes. We report identical twins who presented with polyhydramnios and loss of fetal motility during pregnancy; hypotonia, arthrogryposis and swallowing impairment at birth; need of immediate respiratory support and death at 27 and 50 days of life. Muscle biopsies, performed at 27 days of life in twin 1 and at 49 days in twin 2, showed the presence of separate cores and rods in the muscle fibres, both at light and electron microscopy. The molecular analysis showed a heterozygous de novo mutation (Ile4898Thr) of the RYR1 gene. The molecular study of ACTA1, TMP2 and TMP3 genes did not show abnormalities. This is the first report of a lethal form of congenital "core-rod myopathy". The mutation Ile4898Thr has been previously described in central core disease but not in core-rod myopathy. The report enlarges the phenotypic spectrum of "core-rod myopathy" and highlights the morphological variability associated to special RYR1 mutations.
authors.affiliation: Institut de Myologie, Unité de Morphologie Neuromusculaire, Groupe Hospitalier-Universitaire Pitié-Salpêtrière, Paris F-75013, France.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Hernandez-Lain
authors.forename: Isabelle
authors.initials: I
authors.lastname: Husson
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Caroline
authors.initials: C
authors.lastname: Farnoux
authors.forename: Guy
authors.initials: G
authors.lastname: Brochier
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lacène
authors.forename: Maud
authors.initials: M
authors.lastname: Beuvin
authors.forename: Mait
authors.initials: M
authors.lastname: Viou
authors.forename: Linda
authors.initials: L
authors.lastname: Manéré
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Norma Beatriz
authors.initials: NB
authors.lastname: Romero
mesh_terms: D000199:Actins / Q000235:genetics; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics*; D020512:Myopathy, Central Core / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D014427:Twins / Q000235:genetics*
chemical_list: D000199:Actins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C035620:nebulin