title: Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia.
abstract: We studied seven patients (fetuses/infants) from six unrelated families affected by central core disease (CCD) and presenting with a fetal akinesia syndrome. Two fetuses died before birth (at 31 and 32 weeks) and five infants presented severe symptoms at birth (multiple arthrogryposis, congenital dislocation of the hips, severe hypotonia and hypotrophy, skeletal and feet deformities, kyphoscoliosis, etc.). Histochemical and ultrastructural studies of muscle biopsies confirmed the diagnosis of CCD showing unique large eccentric cores. Molecular genetic investigations led to the identification of mutations in the ryanodine receptor (RYR1) gene in three families, two with autosomal recessive (AR) and one with autosomal dominant (AD) inheritance. RYR1 gene mutations were located in the C-terminal domain in two families (AR and AD) and in the N-terminal domain of the third one (AR). This is the first report of mutations in the RYR1 gene involved in a severe form of CCD presenting as a fetal akinesia syndrome with AD and AR inheritances.
authors.affiliation: Inserm U 582 and Institute of Myology, CHU Pitié-Salpêtrière, Paris, France.
authors.forename: Norma Beatriz
authors.initials: NB
authors.lastname: Romero
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Louis
authors.initials: L
authors.lastname: Viollet
authors.forename: Anne
authors.initials: A
authors.lastname: Cortey
authors.forename: Martine
authors.initials: M
authors.lastname: Chevallay
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Leroy
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005324:Fetal Movement / Q000235:genetics; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009069:Movement Disorders / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D020512:Myopathy, Central Core / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D013577:Syndrome
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel