title: Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients.
abstract: Hereditary spastic paraplegias (HSPs) consist of a heterogeneous group of genetically determined neurodegenerative disorders. Progressive lower extremity weakness and spasticity are the prominent features of HSPs resulting from retrograde axonal degeneration of the corticospinal tracts. Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs). Here, we present the results of genetic testing of the three mentioned SPG genetic types in a group of 216 unrelated Polish patients affected with spastic paraplegia. Molecular evaluation was performed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Nineteen novel mutations: 13 in SPAST, 4 in ATL1 and 2 in REEP1, were identified among overall 50 different mutations detected in 57 families. Genetic analysis resulted in the identification of molecular defects in 54% of familial and 8.4% of isolated cases. Our research expanded the causative mutations spectrum of the three most common genetic forms of HSPs found in a large cohort of probands originating from the Central Europe.
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Elert-Dobkowska
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Stepniak
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Krysa
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Rajkiewicz
authors.affiliation: Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rakowicz
authors.affiliation: Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sobanska
authors.affiliation: Department of Neurology, Medical University of Silesia, Katowice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Rudzinska
authors.affiliation: Department of Neurology, University Hospital, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wasielewska
authors.affiliation: Department of Pediatric Neurology, Medical University of Silesia, Katowice, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Pilch
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kubalska
authors.affiliation: First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Wanda
authors.initials: W
authors.lastname: Lipczynska-Lojkowska
authors.affiliation: First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kulczycki
authors.affiliation: Department of Pediatric Neurology, St. Ludwig's Children Hospital, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kurdziel
authors.affiliation: Department of Genetics and Animal Breeding, University of Life Sciences, Poznan, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Sikorska
authors.affiliation: Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beetz
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland; Division Five of Medical Sciences, Polish Academy of Science, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland. Electronic address: suleka@ipin.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Sulek
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011044:Poland; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C495318:REEP1 protein, human; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human
keywords: ATL1; HSP; Hereditary spastic paraplegias; REEP1; SPAST; SPG