title: Autosomal dominant nemaline myopathy with intranuclear rods due to mutation of the skeletal muscle ACTA1 gene: clinical and pathological variability within a kindred.
abstract: Nemaline Myopathy with Intranuclear Rods is a rare variant of nemaline myopathy, due in almost all instances to mutation of ACTA1, the gene encoding skeletal muscle alpha-actin. We describe the novel autosomal dominant occurrence in a three-generation kindred, and review previously reported cases. Onset of myopathic symptoms in our kindred was in infancy or early childhood. Beyond infancy, limb muscle weakness was non-disabling and minimally progressive. A tall thin face and facial myopathy were prominent features in the affected adults. By light microscopy, muscle biopsies ranged from almost normal, to chronic myopathy with sarcoplasmic and intranuclear rods. A heterozygous GTG-ATG mutation (Val163Met) was found in exon 4 of ACTA1 in affected individuals. Actin is normally present within the nucleus in only trace amounts. Mutation at postion 163 may result in intranuclear rods by virtue of its close proximity to a nuclear export signal within the actin molecule.
authors.affiliation: Department of Neurology, Auckland City Hospital, Private Bag, Auckland 92024, New Zealand. dhutch@adhb.govt.nz
authors.forename: David O
authors.initials: DO
authors.lastname: Hutchinson
authors.forename: Amanda
authors.initials: A
authors.lastname: Charlton
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
authors.forename: Biljana
authors.initials: B
authors.lastname: Ilkovski
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
mesh_terms: D000199:Actins / Q000032:analysis / Q000235:genetics*; D000328:Adult; D001706:Biopsy; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D002675:Child, Preschool; D005091:Exons / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D045586:Intranuclear Inclusion Bodies / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018908:Muscle Weakness / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation; D017696:Myopathies, Nemaline / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D010641:Phenotype
chemical_list: D000199:Actins