Myoclonus-dystonia: Significance of large SGCE deletions

被引：81

作者：

Grunewald, A. ^{[1
,2
]}

Djarmati, A. ^{[1
,2
]}

Lohmann-Hedrich, K. ^{[1
,2
]}

Farrell, K. ^{[3
]}

Zeller, J. A. ^{[4
]}

Allert, N. ^{[5
]}

Papengut, F. ^{[4
]}

Petersen, B. ^{[6
]}

Fung, V. ^{[7
]}

Sue, C. M. ^{[7
,8
,9
]}

O'Sullivan, D. ^{[10
]}

Mahant, N. ^{[7
]}

Kupsch, A. ^{[11
]}

Chuang, R. S. ^{[12
]}

Wiegers, K. ^{[1
,2
]}

Pawlack, H. ^{[1
,2
]}

Hagenah, J. ^{[1
,2
]}

Ozelius, L. J. ^{[13
]}

Stephani, U. ^{[6
]}

Schuit, R. ^{[14
]}

Lang, A. E. ^{[12
]}

Volkmann, J. ^{[4
]}

Munchau, A. ^{[15
]}

Klein, C. ^{[1
,2
]}

机构：

[1] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany

[2] Med Univ Lubeck, Dept Human Genet, Lubeck, Germany

[3] Univ British Columbia, Dept Pediat, Vancouver, BC V5Z 1M9, Canada

[4] Univ Kiel, Dept Neurol, Kiel, Germany

[5] Neurol Rehabil Ctr Godeshohe, Bonn, Germany

[6] Univ Kiel, Dept Neuropediat, Kiel, Germany

[7] Westmead Hosp, Dept Neurol, Westmead, NSW, Australia

[8] Univ Sydney, Royal N Shore Hosp, Dept Neurol, Sydney, NSW 2006, Australia

[9] Univ Sydney, Royal N Shore Hosp, Kolling Inst, Sydney, NSW 2006, Australia

[10] St Vincents Hosp, Darlinghurst, NSW, Australia

[11] Humboldt Univ, Charite Hosp, Berlin, Germany

[12] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON, Canada

[13] Albert Einstein Coll Med, Dept Genet, New York, NY USA

[14] MRC Holland, Amsterdam, Netherlands

[15] Univ Hamburg, Dept Neurol, Hamburg, Germany

来源：

HUMAN MUTATION | 2008年 / 29卷 / 02期

关键词：

COL1A2; deletion; myoclonus-dystonia; MLPA; SGCE;

D O I：

10.1002/humu.9521

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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, pR102X; 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. (C) 2007 Wiley-Liss, Inc.

引用

页码：331 / 332

页数：2