title: Identification of a novel homozygous SPG7 mutation by whole exome sequencing in a Greek family with a complicated form of hereditary spastic paraplegia.
abstract: We report the clinical description and genetic analyses of a Greek family with four individuals affected with a complicated form of hereditary spastic paraplegia (HSP) and a recessive pattern of inheritance. Exome sequencing of all affected individuals led to the identification of a homozygous 25 bp deletion predicted to lead to a frameshift and premature stop codon in the SPG7 gene, encoding paraplegin. This deletion, which is located in the first exon of the SPG7 gene, has not been previously reported and likely lead to the complete absence of the SPG7 protein. Interestingly, this family shows significant phenotypic heterogeneity further highlighting the clinical variability associated with SPG7 mutations. Our findings emphasize the clinical utility of whole exome sequencing for the molecular diagnosis of HSPs.
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.affiliation: University of Patras School of Health Sciences, Department of Pharmacy, University Campus, Patras, Greece.
authors.forename: Eleni Merkouri
authors.initials: EM
authors.lastname: Papadima
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Ouled Amar Bencheikh
authors.affiliation: University of Patras School of Health Sciences, Department of Pharmacy, University Campus, Patras, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Katsila
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: University of Patras School of Health Sciences, Department of Pharmacy, University Campus, Patras, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.affiliation: Genetica Medica, Dipartimento di Scienze Mediche, Università di Cagliari, Cagliari, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Orrù
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: guy.rouleau@mcgill.ca.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018388:Codon, Terminator; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010264:Paraplegia / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree
chemical_list: D018388:Codon, Terminator; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: ARHSP; Frameshift deletion; SPG7; Whole exome sequencing