title: Predominantly upper limb weakness, enlarged cisterna magna, and borderline intelligence in a child with de novo mutation of the skeletal muscle alpha-actin gene.
abstract: We present a 10-year-old boy from nonconsanguineous parents of Libyan (Sephardi) Jewish origin. Mild dysmorphism, hypotonia, and clubfoot deformities were noted at birth. On follow-up, he had borderline intelligence and nonprogressive muscle weakness, predominantly in the upper extremities. Physical examination revealed mild facial weakness, a bell-shaped chest cavity, kyphosis, winging of the scapula, and hypotonia of the shoulder girdle. Muscle biopsy demonstrated prominent variation in fiber size and central nuclei and numerous subsarcolemmal particles on modified Gomori trichrome stains. Electron microscopy depicted areas of disrupted sarcomeres with abnormal aggregates. Brain magnetic resonance imaging showed mild widening of the lateral ventricles and an enlarged cisterna magna. Molecular DNA analysis by polymerase chain reaction (PCR) and direct sequencing revealed a de novo heterozygous missense mutation in the skeletal muscle alpha-actin gene (ACTA1) changing codon 348 from TCG serine to TTG leucine.
authors.affiliation: Child Development Center, Rakati, Tiberias, Israel. origoez@actcom.co.il
authors.forename: Helly
authors.initials: H
authors.lastname: Goez
authors.forename: Liat Ben
authors.initials: LB
authors.lastname: Sira
authors.forename: Joseph
authors.initials: J
authors.lastname: Jossiphov
authors.forename: Zvi
authors.initials: Z
authors.lastname: Borochowitz
authors.forename: Hayley
authors.initials: H
authors.lastname: Durling
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
authors.forename: Yoram
authors.initials: Y
authors.lastname: Nevo
mesh_terms: D000199:Actins / Q000235:genetics*; D001176:Arthrogryposis / Q000235:genetics; D002648:Child; D002946:Cisterna Magna / Q000473:pathology*; D006801:Humans; D007360:Intelligence; D008297:Male; D018908:Muscle Weakness / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology*; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D000199:Actins