title: A novel strumpellin mutation and potential pitfalls in the molecular diagnosis of hereditary spastic paraplegia type SPG8.
abstract: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous, neurodegenerative movement disorder. A total of eight KIAA0196/strumpellin variants have thus far been associated with SPG8, a rare dominant HSP. We present a novel strumpellin alteration in a small family with clinically pure HSP. We corroborated its causality by comparing it to rare benign variants at several levels, and, along this line, also re-considered previous genetic reports on SPG8. These analyses identified significant challenges in the interpretation of strumpellin alterations, and suggested that at least two of the few families claimed to suffer from SPG8 may have been genetically misdiagnosed.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Jahic
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Friedmar
authors.initials: F
authors.lastname: Kreuz
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany; Masters Program General Medicine, Charles University, Prague, Czech Republic.
authors.forename: Pia
authors.initials: P
authors.lastname: Zacher
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Fiedler
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bier
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Reif
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Rieger
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany. Electronic address: christian.beetz@med.uni-jena.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Beetz
authors.affiliation: Gemeinschaftspraxis für Humangenetik, Gutenbergstraße 5, Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Plaschke
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D011506:Proteins; C517003:WASHC5 protein, human
keywords: Hereditary spastic paraplegic; KIAA0196; Pathogenicity prediction; SPG8; Strumpellin