title: Myoclonus-dystonia: significance of large SGCE deletions.
abstract: Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder caused by mutations in SGCE. We investigated the frequency and type of SGCE mutations with emphasis on gene dosage alterations and explored the associated phenotypes. We tested 35 M-D index patients by multiplex ligation-dependent probe amplification (MLPA) and genomic sequencing. Mutations were found in 26% (9/35) of the cases, all but three with definite M-D. Two heterozygous deletions of the entire SGCE gene and flanking DNA and a heterozygous deletion of exon 2 only were detected, accounting for 33% (3/9) of the mutations found. Both large deletions contained COL1A2 and were additionally associated with joint problems. Further, we discovered one novel small deletion (c.771_772delAT, p.C258X) and four recurrent point mutations (c.289C>T, p.R97X; c.304C>T, p.R102X; c.709C>T, p.R237X; c.1114C>T, p.R372X). A Medline search identified 22 articles on SGCE mutational screening. Sixty-four unrelated M-D patients were described with 41 different mutations. No genotype-phenotype association was found, except in patients with deletions encompassing additional genes. In conclusion, a rigorous clinical preselection of patients and careful accounting for non-motor signs should precede mutational tests. Gene dosage studies should be included in routine SGCE genetic testing.
authors.affiliation: Department of Neurology, Lübeck University, Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Grünewald
authors.forename: A
authors.initials: A
authors.lastname: Djarmati
authors.forename: K
authors.initials: K
authors.lastname: Lohmann-Hedrich
authors.forename: K
authors.initials: K
authors.lastname: Farrell
authors.forename: J A
authors.initials: JA
authors.lastname: Zeller
authors.forename: N
authors.initials: N
authors.lastname: Allert
authors.forename: F
authors.initials: F
authors.lastname: Papengut
authors.forename: B
authors.initials: B
authors.lastname: Petersen
authors.forename: V
authors.initials: V
authors.lastname: Fung
authors.forename: C M
authors.initials: CM
authors.lastname: Sue
authors.forename: D
authors.initials: D
authors.lastname: O'Sullivan
authors.forename: N
authors.initials: N
authors.lastname: Mahant
authors.forename: A
authors.initials: A
authors.lastname: Kupsch
authors.forename: R S
authors.initials: RS
authors.lastname: Chuang
authors.forename: K
authors.initials: K
authors.lastname: Wiegers
authors.forename: H
authors.initials: H
authors.lastname: Pawlack
authors.forename: J
authors.initials: J
authors.lastname: Hagenah
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: U
authors.initials: U
authors.lastname: Stephani
authors.forename: R
authors.initials: R
authors.lastname: Schuit
authors.forename: A E
authors.initials: AE
authors.lastname: Lang
authors.forename: J
authors.initials: J
authors.lastname: Volkmann
authors.forename: A
authors.initials: A
authors.lastname: Münchau
authors.forename: C
authors.initials: C
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003710:Demography; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009207:Myoclonus / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012196:Review Literature as Topic; D049031:Sarcoglycans / Q000235:genetics*
chemical_list: D049031:Sarcoglycans