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Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder

Published online by Cambridge University Press:  09 July 2009

M. C. O'Donovan*
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
C. Guy
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
N. Craddock
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
T. Bowen
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
P. McKeon
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
A. Macedo
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
W. Maier
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
D. Wildenauer
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
H. N. Aschauer
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
S. Sorbi
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
E. Feldman
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
L. Mynett-Johnson
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
E. Claffey
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
B. Nacmias
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
J. Valente
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
A. Dourado
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
E. Grassi
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
E. Lenzinger
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
A. M. Heiden
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
S. Moorhead
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
D. Harrison
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
J. Williams
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
P. McGuffin
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
M. J. Owen
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff and Department of Psychiatry, Queen's Medical Centre, University of Nottingham; Depression Research Unit, St Patrick's Hospital and Trinity College, Dublin, Ireland; Department of Psychiatry, Faculdade de Medicina, Universida de Coimbra, Portugal; Psychiatrische Universitätsklinik, Bonn and Psychiatrische Klinik der Universität Munchen, Germany; Psychiatrische Universitätsklinik, Universität Wien, Austria; and Department of Neurological Science, University of Florence, Italy
*
1Address for correspondence: Dr Michael O'Donovan, Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN.

Synopsis

Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1996

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References

American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. Revised. American Psychiatric Association: Washington, DC.Google Scholar
Asherson, P., Walsh, C., Williams, J., Sargeant, M., Taylor, C., Clements, A., Gill, M., Owen, M. & McGuffin, P. (1994). Imprinting and anticipation – are they relevant to genetic studies of schizophrenia? British Journal of Psychiatry 164, 619624.Google Scholar
Bassett, A. S. & Honer, W. G. (1994). Evidence for anticipation in schizophrenia. American Journal of Human Genetics 54, 864870.Google Scholar
Endicott, J. & Spitzer, R. L. (1978). A diagnostic interview. The Schedule for Affective Disorders and Schizophrenia. Archives of General Psychiatry 35, 837844.CrossRefGoogle ScholarPubMed
Fu, Y. H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkerk, A. J. M. H., Holden, J. J. A., Fenwick, R. G. Jr., Warren, S. T., Oostra, B. A., Nelson, D. L. & Caskey, C. T. (1991). Variation of the CGG repeat at the fragile-X site results in genetic instability: resolution of the Sherman paradox. Cell 67, 10471058.CrossRefGoogle ScholarPubMed
Gastier, J. M., Brody, T., Pulido, J. C., Businga, T., Sunden, S., Hu, X., Maitra, S., Buetow, K. H., Murray, J. C., Sheffield, V. C., Boguski, M., Duyk, G. M. & Hudson, T. J. (1996). Development of a screening set for new (CAG/CTG)n dynamic mutations. Genomics 32, 7485.CrossRefGoogle ScholarPubMed
Haaf, T., Sirugo, G., Kidd, K. K. & Ward, D. C. (1996). Chromosomal location of long trinucleotide repeats in the human genome by fluorescence in situ hybridization. Nature Genetics 12, 183185.Google Scholar
Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's Disease chromosomes. Cell 72, 971983.CrossRefGoogle Scholar
Kawaguci, Y., Okamoto, T., Taniwaki, M., Aizawa, M., Inoue, M., Katayama, S., Kawakami, H., Nakamura, S., Nishimura, M., Akiguchi, I., Kimura, J., Narumiya, S. & Kakizuka, A. (1994). CAG expansions in a novel gene for machado-Joseph disease at chromosome 14q32.1. Nature Genetics 8, 221228.Google Scholar
Khoury, M. J., Beaty, T. H. & Cohen, B. H. (1993). Fundamentals of Genetic Epidemiology, Monographs in Epidemiology and Biostatistics. Vol 19. Oxford University Press: Oxford.Google Scholar
Li, S. H., McInnis, M. G., Margolis, R. L., Antonarakis, S. E. & Ross, C. A. (1993). Novel triplet repeat containing genes in human brain: cloning, expression, and length polymorphism. Genomics 16, 572579.Google Scholar
Lindblad, K., Nylander, P.-O., De bruyn, A., Sourey, D., Zander, C., Engstrom, C., Holmgren, G., Hudson, T., Chotai, J., Mendlewicz, J., Van Broeckhoven, C., Schalling, M. & Adolfsson, R. (1995). Detection of expanded CAG repeats in Bipolar Affective Disorder using the repeat expansion detection (RED) method. Neurobiology of Disease 2, 5562.CrossRefGoogle ScholarPubMed
Margolis, R. L., Stine, O. C., McInnis, M. G., Ranen, N. G., Rubinsztein, D. C.,. Leggo, J., Jones Brando, L. V., Kidwai, A. S., Loev, S. J., Breschel, T. S., Callahan, C., Simpson, S. G., Depaulo, J. R., McMahon, F. J., Jain, S., Paykel, E. S., Walsh, C., DeLisi, L. E., Crow, T. J., Torrey, E. F., Ashworth, R. G., Macke, J. P., Nathans, J. & Ross, C. A. (1996). cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat. Human Molecular Genetics 5, 607616.CrossRefGoogle ScholarPubMed
McGuffin, P., Farmer, A. & Harvey, I. (1991). A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Archives of General Psychiatry 48, 764770.Google Scholar
McGuffin, P., Asherson, P., Owen, M. & Farmer, A. (1994 a). The strength of the genetic effect – is there room for an environmental influence in the aetiology of schizophrenia? British Journal of Psychiatry 164, 593599.CrossRefGoogle ScholarPubMed
McGuffin, P., Owen, M. J., O'Donovan, M. C., Thapar, A. & Gottesman, I. I. (1994 b). Seminars in Psychiatric Genetics. Royal College of Psychiatrists: London.Google Scholar
McInnis, M. G., McMahon, F. J., Chase, G. A., Simpson, S. G., Ross, C. A. & Depaulo, J. R. Jr (1993). Anticipation in bipolar affective disorder. American Journal of Human Genetics 53, 385390.Google ScholarPubMed
Morris, A. G., Gaitonde, E., McKenna, P. J., Mollon, J. D. & Hunt, D. M. (1995). CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset. Human Molecular Genetics 4, 19571961.CrossRefGoogle ScholarPubMed
Nurnberger, J. I. Jr, Blehar, M. C., Kaufmann, C. A., York-Coller, C., Simpson, S. G., Harkavy-Friedman, J., Severe, J. B., Malaspina, D., Reich, T. & Collaborators from the NIMH Genetics Initiative (1994). Diagnostic Interview for Genetic Studies: rationale, unique features and training. Archives of General Psychiatry 51, 849864.Google Scholar
Nylander, P. O., Engstrom, C., Chotai, J., Wahlstrom, J. & Adolfsson, R. (1994). Anticipation in Swedish families with bipolar affective disorder. Journal of Medical Genetics 31, 686689.CrossRefGoogle ScholarPubMed
O'Donovan, M. C. & Owen, M. J. (1996) Dynamic mutations and psychiatric genetics. Psychological Medicine 26, 16.Google Scholar
O'Donovan, M. C., Guy, C., Craddock, N., Murphy, K. C., Cardno, A. G., Jones, L. A., Owen, M. J. & McGuffin, P. (1995). Expanded CAG repeats in schizophrenia and bipolar disorder. Nature Genetics 10, 380381.CrossRefGoogle ScholarPubMed
Petronis, A. & Kennedy, J. L. (1995). Unstable genes – unstable mind. American Journal of Psychiatry 152, 164172.Google Scholar
Robins, L. N., Wing, J., Wittchen, H. V., Helzer, J. E., Babor, T. F., Burke, J., Farmer, A. E., Jablenski, A., Picken, R., Regier, D. A., Sartorius, N. & Towle, L. H. (1988). The Composite International Diagnostic Interview: an epidemiological instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Archives of General Psychiatry 45, 10691078.Google Scholar
Schalling, M., Hudson, T. J., Buetow, K. H. & Housman, D. E. (1993). Direct detection of novel expanded trinucleotide repeats in human genome. Nature Genetics 4, 135139.CrossRefGoogle ScholarPubMed
Sirugo, G. & Kidd, K. K. (1995). Repeat expansion detection using Ampligase thermostable DNA ligase. Epicenter Forum 2, 13.Google Scholar
Snell, R. G., MacMillan, J. C., Cheadle, J. P., Fenton, I., Lazarou, L. P., Davies, P., MacDonald, M. E., Gusella, J. F., Harper, P. S. & Shaw, D. J. (1993). Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nature Genetics 4, 393397.Google Scholar
Thibaut, F., Martinez, M., Petit, M., Jay, M. & Campion, D. (1995). Further evidence for anticipation in schizophrenia. Psychiatry Research 59, 2533.Google Scholar
Wing, J. K., Cooper, J. E., Sartorius, N. (1972). Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: Cambridge.Google Scholar
Wing, J. K., Babor, T., Brugha, T., Burke, J., Cooper, J. E., Giel, R., Jablenski, A., Reigier, D. & Sartorius, N. (1990). Schedules for clinical assessment in neuropsychiatry. Archives of General Psychiatry 47, 589593.Google Scholar
Yu, S., Pritchard, M., Kremer, E., Lynch, M., Nancarrow, J., Baker, E., Holman, K., Mulley, J. C., Warren, S. T., Schlessinger, D., Sutherland, G. R. & Richards, R. I. (1991). Fragile-X genotype characterized by an unstable region of DNA. Science 252, 11791181.CrossRefGoogle ScholarPubMed