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Nucleotide and protein expansions and human disease
  1. D C Rubinsztein

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    Edited by J Gecz, G R Sutherland. Basel: Karger publishers, Reprint of Cytogenetic and Genome Research Vol 100 Nos 1–4, 2003, £67.50, pp 298. ISBN 3-8055-7621-8 (hardback)

    Since 1991, when the CAG repeat expansion causing spinobulbar muscular dystrophy and the CCG repeat expansion in fragile X syndrome were discovered, there has been great progress in understanding the biology of triplet repeat instability and the diseases associated with these types of mutation. The number of diseases and classes of mutations has grown such that there are currently nine CAG repeat diseases where the repeats are translated into polyglutamine tracts, a recessive triplet mutation (Friedreich’s ataxia), more than a handful of different diseases caused by expanded polyalanine tracts (for example, oculopharyngeal muscular dystrophy), diseases associated with untranslated triplet repeats (for example, myotonic dystrophy), and diseases caused by expansion of other micro or minisatellites (for example, progressive myoclonus epilepsy).

    Soon after the first group of triplet repeat mutations was discovered, the biological mechanism was revealed behind the previously baffling (and controversial) phenomenon of anticipation, where the disease tends to increase in severity or present at an earlier age in successive generations in families. In many cases there has been rapid progress in developing cell and animal models of disease, and in some cases we have a much better understanding of pathogenesis. Yet many mysteries and controversies remain, even for diseases where the mutation was identified a decade or so ago (for example, myotonic dystrophy and Huntington’s disease) and cures and treatments for the human diseases are still elusive.

    This book addresses certain aspects of the field with a collection of freestanding articles covering aspects ranging from trinucleotide repeat instability, through epidemiology of spinocerebellar ataxias, to pathogenetic mechanisms. The nature of the book means that there are sometimes issues that are duplicated between chapters. This is not a problem, as the book is probably not designed to be read from cover to cover, but rather as a reference source. The topic coverage is not complete and gaps include discussions of the pathogenesis of Friedreich’s ataxia and spinocerebellar ataxia type 1 (both where considerable progress has been made). However, in contrast to many other books where there are collections of chapters, for instance focused on neurological diseases, this book deals with some of the more esoteric areas very well. There are fine chapters on repeat instability (by Lenzmeier and Freudenreich; and by Cleary and Pearson), oculopharyngeal muscular dystrophy (Brais) and on transgenic models of myotonic dystrophy (Wansink and Wieringa), spinobulbar muscular dystrophy (Sobue and colleagues), Huntington’s disease (Hickey and Chesselet) and Fragile X syndrome (Bakker and Oostra). It was good to see a chapter devoted to the interesting and possibly under recognised cerebellar ataxia syndrome associated with FRAXA premutation carriers (Hagerman et al) and the excellent chapter on SCA3 by Kobayashi and Kakizuka (a group that have made a number of key contributions to the polyglutamine disease field). In general, the chapters are written by authorities in their fields (including Brice, Ashizawa, Margolis, La Spada, Nelson, Usdin, and Ranum).

    In conclusion, this book includes many chapters that add to and complement existing texts dealing with these diseases. The articles are generally of a high standard and are concisely written. This book would be of particular value to human geneticists, genetic counsellors, and researchers working on this class of diseases.

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