title: ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia.
abstract: Silver syndrome/SPG17 is a motor manifestation of mutations in the BSCL2 gene and usually presents as a complicated form of hereditary spastic paraplegia (HSP). We present clinical data, follow-up, and genetic results of seven patients with Silver syndrome/SPG17 including a family with a variable intrafamilial phenotype ranging from subclinical signs to a severe and rapidly progressing amyotrophic lateral sclerosis (ALS)-like phenotype. For molecular diagnosis of the family, we used the TruSight Exome sequencing panel consisting of 2761 genes. We filtered for variants common to affected family members and for exclusive variants in the ALS-like index patient to find possible modifier mutations. We found that de novo mutations and/or incomplete penetrance in BSCL2 has been taken into account for Silver syndrome/SPG17 and confirm the large phenotypical heterogeneity of BSCL2 mutations. Our findings broaden the reported spectrum of the disease to an ALS-like and multifocal motor neuropathy phenotype and underline the need for further research for genetic modifiers due to the striking interindividual and intrafamilial variability.
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Musacchio
authors.affiliation: Department of Human Genetics, University of Würzburg, Würzburg, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Zaum
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Pfeifroth
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Reiners
authors.affiliation: Department of Human Genetics, University of Würzburg, Würzburg, Germany.
authors.forename: Erdmute
authors.initials: E
authors.lastname: Kunstmann
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Volkmann
authors.affiliation: Department of Human Genetics, University of Würzburg, Würzburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Rost
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany. stephan.klebe@uniklinik-freiburg.de.|Department of Neurology, University Hospital Freiburg, Freiburg, Germany. stephan.klebe@uniklinik-freiburg.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D055815:Young Adult
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits
keywords: BSCL2; Hereditary spastic paraplegia; SPG17