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Dynamic Mutations

Where Are They Now?

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Tandem Repeat Polymorphisms

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Dynamic mutations are those caused by the expansion of existing polymorphic DNA repeat sequences beyond a copy number threshold. These genetic mutations can give rise to dominant, recessive or X-linked disorders, dependent upon the location of the repeat sequence with respect to the genes that are affected by the expansion. The distinguishing feature of these mutations is their instability, which is a function of the copy number of repeats and can occur in either meiosis or mitosis. For some of the resultant disorders there is a relationship between repeat copy number and age-at-onset and/or severity of symptoms of the disease.For this reason much effort is now focused on identifying the pathogenic pathways from the mutation to the disease symptoms in the hope of finding means of delaying onset, slowing progression or even preventing symptoms of the disease. The growing list of neuro degenerative and neuromuscular diseases caused by dynamic mutations includes Huntington’ s disease (HD), spinobulbar muscular atrophy (SBMA),dentatorubral-pallidoluysian atrophy (DRPLA), a number of spinocerebellar ataxias (SCAs), oculopharyngeal muscular dystrophy (OPMD), myotonic dystrophy Type 1 and 2 (DM1 and 2), Huntington’s disease-like 2 (HDL-2), Friedrich’s ataxia (FRDA), Fragile X associated tremor ataxia syndrome (FXTAS), Fragile XE (FRAXE) and Fragile XA (FRAXA). This chapter aims to give a brief overview of what is currently known about each disease and the mechanisms underlying pathogenesis.

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  1. Discipline of Genetics, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, South Australia, Australia

    Clare L. van Eyk & Robert I. Richards

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  1. Clare L. van Eyk
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Correspondence to Clare L. van Eyk .

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  1. Florey Neuroscience Institutes, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia

    Anthony J. Hannan Phd

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van Eyk, C.L., Richards, R.I. (2012). Dynamic Mutations. In: Hannan, A.J. (eds) Tandem Repeat Polymorphisms. Advances in Experimental Medicine and Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5434-2_5

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