Unbalanced whole arm translocation resulting in loss of 18p in dystonia

Authors

  • Jamal Nasir PhD,

    Corresponding author
    1. Academic Neurology Unit, Section of Genetics and Informatics, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom
    • Academic Neurology Unit, Section of Genetics and Informatics, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, United Kingdom
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  • Nafsika Frima PhD,

    1. Academic Neurology Unit, Section of Genetics and Informatics, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom
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  • Ben Pickard PhD,

    1. Medical Genetics, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
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  • M. Pat Malloy,

    1. Medical Genetics, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
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  • Lingping Zhan MD, PhD,

    1. Academic Neurology Unit, Section of Genetics and Informatics, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom
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  • Richard Grünewald DPhil, FRCP

    1. Academic Neurology Unit, Section of Genetics and Informatics, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom
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Abstract

Dystonia represents a genetically and clinically heterogeneous disorder, characterized by abnormal and sustained muscle contractions and rigid postures. At least 15 different loci (DYT1–DYT15) have been identified in dystonia. Adult-onset idiopathic focal dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp), is mostly associated with the DYT7 locus, which was originally mapped to chromosome 18p by genomewide linkage analysis in a large family showing autosomal dominant inheritance. We have identified a family in which the mother is affected with dystonia and the son shows signs of dystonia. Using fluorescent BAC probes spanning 18p, we were able to identify a deletion in these two individuals, spanning the entire short arm of 18p. This deletion is accompanied by a centric fusion involving chromosome 14. The 18p deleted region spans 15 megabases of DNA, with a number of interesting DYT7 candidate genes, including genes involved in G-protein–coupled signaling (GNAL), cell death (CIDEA), muscle development (MYOM1 and MRLM), mitochondrial activity (NDUFV2), and neuronal function (ADYCAP1, TGIF, DAP-1, and AFG3L2). © 2006 Movement Disorder Society

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