title: Autosomal recessive hereditary spastic paraplegia-clinical and genetic characteristics of a well-defined cohort.
abstract: We describe the clinical and genetic features of a well-characterized cohort of patients with autosomal recessive hereditary spastic paraplegia (ARHSP) in the province of Ontario. Patients with documented corticospinal tract abnormalities were screened by whole gene sequencing and multiplex ligation probe amplification for mutations in nine genes known to cause ARHSP. Of a cohort of 39 patients, a genetic diagnosis was established in 17 (44 %) and heterozygous mutations were detected in 8 (21 %). Mutations were most frequent in SPG7 (12 patients), followed by SPG11 (10 patients), PNPLA6 (SPG39, 2 patients), and ZFYVE26 (SPG15, 2 patients). Although there are associations between some clinical manifestations of ARHSP and specific genes, many patients are tested at an early stage of the disease when phenotype/genotype correlations are not obvious. Accurate molecular characterization of well-phenotyped cohorts of patients will be essential to establishing the natural history of these rare degenerative disorders to enable future clinical trials.
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada, grace.yoon@utoronto.ca.
authors.forename: G
authors.initials: G
authors.lastname: Yoon
authors.forename: B
authors.initials: B
authors.lastname: Baskin
authors.forename: M
authors.initials: M
authors.lastname: Tarnopolsky
authors.forename: K M
authors.initials: KM
authors.lastname: Boycott
authors.forename: M T
authors.initials: MT
authors.lastname: Geraghty
authors.forename: E
authors.initials: E
authors.lastname: Sell
authors.forename: S
authors.initials: S
authors.lastname: Goobie
authors.forename: W
authors.initials: W
authors.lastname: Meschino
authors.forename: B
authors.initials: B
authors.lastname: Banwell
authors.forename: P N
authors.initials: PN
authors.lastname: Ray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011712:Pyramidal Tracts / Q000473:pathology; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D055815:Young Adult