Myoclonus-dystonia: significance of large SGCE deletions.
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Myoclonus-dystonia: significance of large SGCE deletions. / Grünewald, A; Djarmati, A; Lohmann-Hedrich, K; Farrell, K; Zeller, J A; Allert, N; Papengut, F; Petersen, B; Fung, V; Sue, C M; O'Sullivan, D; Mahant, N; Kupsch, A; Chuang, R S; Wiegers, K; Pawlack, H; Hagenah, J; Ozelius, L J; Stephani, U; Schuit, R; Lang, A E; Volkmann, J; Münchau, Alexander; Klein, C.
in: HUM MUTAT, Jahrgang 29, Nr. 2, 2, 2008, S. 331-332.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Myoclonus-dystonia: significance of large SGCE deletions.
AU - Grünewald, A
AU - Djarmati, A
AU - Lohmann-Hedrich, K
AU - Farrell, K
AU - Zeller, J A
AU - Allert, N
AU - Papengut, F
AU - Petersen, B
AU - Fung, V
AU - Sue, C M
AU - O'Sullivan, D
AU - Mahant, N
AU - Kupsch, A
AU - Chuang, R S
AU - Wiegers, K
AU - Pawlack, H
AU - Hagenah, J
AU - Ozelius, L J
AU - Stephani, U
AU - Schuit, R
AU - Lang, A E
AU - Volkmann, J
AU - Münchau, Alexander
AU - Klein, C
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 29
SP - 331
EP - 332
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 2
M1 - 2
ER -
