title: Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia.
abstract: We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G>T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy.
authors.affiliation: Department of Pediatric Neurology, Schneider Children's Medical Center of Israel, 14 Kaplan St., 49202, Petach Tikva, Israel, brosh3826@bezeqint.net.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Halevy
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Rony
authors.initials: R
authors.lastname: Cohen
authors.forename: Liora
authors.initials: L
authors.lastname: Kornreich
authors.forename: Avinoam
authors.initials: A
authors.lastname: Shuper
authors.forename: Moria
authors.initials: M
authors.lastname: Gamliel
authors.forename: Bat-El
authors.initials: BE
authors.lastname: Zimerman
authors.forename: Isam
authors.initials: I
authors.lastname: Korabi
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: C571397:EXOSC3 protein, human; D016601:RNA-Binding Proteins; D063326:Exosome Multienzyme Ribonuclease Complex