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The Genetics of Mental Retardation

Published online by Cambridge University Press:  02 January 2018

Anita Thapar ,
Irving I. Gottesman ,
Michael J. Owen ,
Michael C. O'Donovan  and
Peter McGuffin
Anita Thapar*
Affiliation:
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN
Irving I. Gottesman
Affiliation:
Department of Psychology, University of Virginia, Charlottesville, VA, USA
Michael J. Owen
Affiliation:
Department of Psychological Medicine and Institute of Medical Genetics, University of Wales College of Medicine, Cardiff
Michael C. O'Donovan
Affiliation:
Center for Cancer Research, Massachussetts Institute of Technology, Cambridge, MA 02139, USA
Peter McGuffin
Affiliation:
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff
*
∗Correspondence
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Abstract

Individuals affected by mental retardation are a clinically and aetiologically heterogeneous group. This heterogeneity is particularly highlighted when we consider the genetics of mental retardation. Recent advances in molecular genetic techniques have enabled us to understand more about the molecular basis of several genetic syndromes associated with mental retardation. In contrast, where there is no discrete cause, the interplay of genetic and environmental influences remains poorly understood.

Type
Papers
Information
The British Journal of Psychiatry , Volume 164 , Issue 6 , June 1994 , pp. 747 - 758
Copyright
Copyright © 1994 The Royal College of Psychiatrists 

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References

Akesson, H. O. (1986) The biological origin of mild mental retardation. Acta Psychiatrica Scandinavica, 74, 3–7.Google Scholar
Angelman, H. (1965) Puppet children. Developmental Medicine and Child Neurology, 7, 681–688.Google Scholar
Bouchard, T. J. & McGue, M. (1981) Familial studies of intelligence: a review. Science, 212, 1055–1059.Google Scholar
Brown, W. T., Jenkins, E., Neri, G., et al (1991) Conference report: Fourth International Workshop on the fragile X and X-linked mental retardation. American Journal of Medical Genetics, 38, 158–172.Google Scholar
Bundey, S., Thake, A. & Todd, J. (1989) The recurrence risks for mild idiopathic mental retardation. Journal of Medical Genetics, 26, 260–266.Google Scholar
Butler, M. (1990) Prader–Willi Syndrome: current understanding of cause and diagnosis. American Journal of Medical Genetics, 35, 319–332.Google Scholar
Capron, C. & Duyme, M. (1989) Assessment of effects of socioeconomic status on IQ in a full cross-fostering study. Nature, 340, 552–553.CrossRefGoogle Scholar
Carothers, A. D. & Filippi, G. (1988) Klinefelter's syndrome in Sardinia and Scotland. Human Genetics, 81, 71–75.Google Scholar
Cassidy, S. B. (1987) Recurrence risk in Prader-Willi syndrome. American Journal of Medical Genetics, 28, 59–60.CrossRefGoogle ScholarPubMed
Chudley, A. E., Knoll, J., Gerrard, J. W., et al (1983) Fragile (X) X linked mental retardation. I: Relationship between age and intelligence and the frequency of expression of fragile (X) (q28). American Journal of Medical Genetics, 14, 699–712.Google Scholar
Clayton-Smith, J., Webb, T., Malcolm, S., et al (1991) Genetic mechanisms and recurrence risks in Angelman's syndrome. Journal of Medical Genetics, 28, 568A.Google Scholar
Clayton-Smith, J., & Pembrey, M. E. (1992) Angelman syndrome. Journal of Medical Genetics, 29, 412–415.Google Scholar
Clayton-Smith, J., Webb, T., Robb, S. A., et al (1992) Further evidence for dominant inheritance at the chromosome 15q11–13 locus in familial Angelman syndrome. American Journal of Medical Genetics, 44, 256–260.CrossRefGoogle ScholarPubMed
Davies, K. E. (1992) The costs of instability. Nature, 356, 15.Google Scholar
Ellison, K. A., Fill, C. P., Terwilliger, J., et al (1992) Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis. American Journal of Human Genetics, 50, 278–287.Google Scholar
Fisch, G. S. (1992) Is autism associated with the fragile X syndrome? American Journal of Medical Genetics, 43, 47–55.Google Scholar
Freund, L. S., Reiss, A. L., Hagerman, R., et al (1992) Chromosome fragility and psychopathology in obligate female carriers of the fragile X chromosome. Archives of General Psychiatry, 49, 54–60.CrossRefGoogle ScholarPubMed
Fryns, J. P. (1986) The female and the fragile X. A study of 144 obligate female carriers. American Journal of Medical Genetics, 23, 157–169.CrossRefGoogle Scholar
Fu, Y. H., Kuhl, D. P. A., Pizzuti, A., et al (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell, 67, 1–20.CrossRefGoogle ScholarPubMed
Gilberg, C., Wahlstrom, J. & Hagberg, B. (1985) A new chromosome marker common to RCH syndrome and infantile autism? The frequency of fragile sites at Xp22 in 81 children with infantile autism, childhood psychosis and the RCH syndrome. Brain Development, 7, 365–367.Google Scholar
Glass, I. (1991) X linked mental retardation. Journal of Medical Genetics, 28, 361–371.CrossRefGoogle ScholarPubMed
Goate, A., Chartier-Harlin, M.-C., Mullan, M., et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349, 704–706.CrossRefGoogle ScholarPubMed
Gostason, R., Wahlstrom, J., Johannisson, T., et al (1991) Chromosomal aberrations in the mildly mentally retarded. Journal of Mental Deficiency Research, 35, 240–246.Google Scholar
Gottesman, I. I. (1971) An introduction to behavioral genetics of mental retardation. In Role of Genetics in Mental Retardation (eds Allen, R. M. et al), pp. 49–69. Coral Gables: University of Miami.Google Scholar
Guthrie, R. & Susi, A. (1963) A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics, 32, 338–343.CrossRefGoogle ScholarPubMed
Guttler, F. (1984) Phenylketonuria: 50 years since Folling's discovery and still expanding our clinical and biochemical knowledge. Acta Paediatrica Scandinavica, 73, 705–716.Google Scholar
Hagberg, B. (1985) Rett syndrome: A Swedish approach to analysis of prevalence and cause. Brain Development, 7, 277–280.Google Scholar
Hagberg, B., Hagberg, G., Lewerth, A., et al (1981) Mild mental retardation in Swedish schoolchildren II. Etiologic and pathogenetic aspects. Acta Paediatrica Scandinavica, 70, 445–452.Google Scholar
Hagberg, B., Aicardi, J., Dias, K., Ramos, O. (1983) A progressive syndrome of autism, dementia, ataxia and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Annals of Neurology, 14, 471–479.Google Scholar
Hagberg, B., & Hagberg, G. (1984) Aspects of prevention of pre-, peri- and postnatal brain pathology in severe and mild mental retardation. In Scientific Studies in Mental Retardation (eds Dobbing, J., Clarke, A. D. B., Corbett, J. A., et al) pp. 43–64. London/Basingstoke: Royal Society of Medicine/Macmillan.CrossRefGoogle Scholar
Hagerman, R. J. & Sobesky, W. E. (1989) Psychopathology in fragile X syndrome. American Journal of Orthopsychiatry, 59, 142–152.Google Scholar
Hilbert, P. Lindpaintner, K., Beckmann, J. S., et al (1991) Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature, 353, 521–529.CrossRefGoogle ScholarPubMed
Hook, E. B. (1973) Behavioral implications of the human XYY genotype. Science, 179, 139–179.Google Scholar
Horn, J. M., Loehlin, J. C. & Willerman, L. (1979) Intellectual resemblance among adoptive and biological relatives: the Texas Adoption Project. Behavioral Genetics, 9, 177–207.Google Scholar
Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable in Huntington's Disease chromosomes. Cell, 72, 1–20.Google Scholar
Jacobs, P. A., Price, W. H., Cower-Brown, W. M., et al (1968) Chromosome studies on men in maximum security hospitals. Annals of Human Genetics, 31, 339–358.CrossRefGoogle Scholar
Kerr, A. M. & Stephenson, J. B. P. (1985) Rett's syndrome in the West of Scotland. British Medical Journal, 291, 579–582.Google Scholar
Knoll, J. H. M., Nicholls, R. D., Magenis, R. E., et al (1989) Angelman and Prader-Willi syndrome share a common chromosome 15 deletion but differ in parental origin of the deletion. American Journal of Medical Genetics, 32, 285–290.Google Scholar
Konecki, D. S. & Lichter-Konecki, U. (1991) The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Human Genetics, 87, 377–388.CrossRefGoogle ScholarPubMed
Korenberg, J. R., Kawashima, H., Pulst, S. M., et al (1990) Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. American Journal of Human Genetics, 47, 236–246.Google Scholar
Kwok, S. C. M., Ledley, F. D., DiLella, A. G., et al (1985) Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry, 24, 556–561.CrossRefGoogle ScholarPubMed
Lancet (1991) Editorial. Phenylketonuria grows up. Lancet, 337, 1256–1257.Google Scholar
Ledley, F. D., Grenett, H. E., DiLella, A. G., et al (1985) Gene transfer and expression of human phenylalanine hydroxylase. Science, 228, 77–79.Google Scholar
Leff, S. E., Brannan, C. I., Reed, M. L., et al (1992) Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader–Willi syndrome region. Nature Genetics, 2, 259–264.CrossRefGoogle ScholarPubMed
Lidsky, A. S., Law, M. L., Morse, H. G., et al (1985) Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome. Proceedings of the National Academy of Sciences of the USA, 82, 6221–6225.Google Scholar
Loehlin, J. C., Willerman, L. R., Horn, J. M. (1988) Human behavior genetics. Annual Reviews in Psychology, 39, 101–133.Google Scholar
McCormick, M. K., Schinzel, A., Petersen, M. B., et al (1989) Molecular genetics approach to the characterization of the “Down syndrome region” of chromosome 21. Genomics, 5, 325–331.Google Scholar
McKusick, V. A. & Amberger, J. S. (1993) The morbid anatomy of the human genome: chromosomal location of mutations causing disease. Journal of Medical Genetics, 30, 1–26.CrossRefGoogle ScholarPubMed
Malcolm, S., Clayton-Smith, J., Nichols, M., et al (1991) Uniparental disomy in Angelman syndrome. Lancet, 337, 694–697.Google Scholar
Mandel, J. L., Hagerman, R., Froster, U., et al (1992) Fifth International Workshop on the Fragile X and X linked mental retardation. American Journal of Medical Genetics, 43, 5–27.Google Scholar
Mandoki, M. W., Sumner, G. S., Hoffman, R. P., et al (1991) A review of Klinefelter's syndrome in children and adolescents. Journal of the American Academy of Child and Adolescent Psychology, 30, 167–172.Google Scholar
Martinho, P. S., Otto, P. G., Kok, F., et al (1990) In search of a genetic basis for the Rett syndrome. Human Genetics, 86, 131–134.CrossRefGoogle ScholarPubMed
Meijers-Heijboer, E. J., Sandkuijl, L. A., Brunner, H. G. et al (1992) Linkage analysis with chromosome 15q11–13 markers shows genomic imprinting in familial Angelman syndrome. Journal of Medical Genetics, 29, 853–857.Google Scholar
Neri, G., Chiurazzi, P., Arena, F., et al (1992) XLMR genes: Update 1992. American Journal of Medical Genetics, 43, 373–382.Google Scholar
Nicholls, R. D., Knoll, J. H. M., Butler, M. G., et al (1989) Genetic imprinting suggested by maternal heterodisomy in non deletion Prader-Willi syndrome. Nature, 342, 281–285.Google Scholar
Nichols, P. L. (1984) Familial mental retardation. Behavior Genetics, 14, 161–170.Google Scholar
Oberle, I., Rousseau, F., Heitz, D., et al (1991) Instability of a 550 base pair DNA segment and abnormal methylation in fragile X syndrome. Science, 252, 1097–1102.CrossRefGoogle ScholarPubMed
Okano, Y., Eisensmith, R., Guttler, E., et al (1991) Molecular basis of phenotypic heterogeneity in PKU. New England Journal of Medicine, 324, 1232–1238.Google Scholar
Özcelik, T., Leff, S., Robinson, W., et al (1992) Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genetics, 2, 265–269.Google Scholar
Penrose, L. S. (1938) A clinical and genetic study of 1,280 cases of mental defect. Special Report Series 229. London: Medical Research Council.Google Scholar
Pergolizzi, R. G., Erster, S. H., Goonewardeena, P., et al (1992) Detection of full fragile X mutation. Lancet, 339, 271–272.Google Scholar
Plomin, R. (1990) The role of inheritance in behaviour. Science, 248, 183–188.Google Scholar
Plomin, R., DeFries, J. C. & Fulker, D. W. (1988) Nature and Nurture in Infancy and Early Childhood. New York: Cambridge University Press.Google Scholar
Plomin, R., & Rende, R. (1991) Human behavioural genetics. Annual Reviews in Psychology, 42, 161–190.CrossRefGoogle Scholar
Rahmani, Z., Blouin, J. L., Creau-Goldberg, N., et al (1990) Down syndrome critical region around D21S55 on proximal 21q22.3. American Journal of Medical Genetics (suppl.) 7, 98–103.Google Scholar
Reed, E. W. & Reed, S. C. (1965) Mental Retardation: A Family Study. Philadelphia: W. B. Saunders.Google Scholar
Reiss, A. L., Hagerman, R., Vinogradov, S., et al (1988) Psychiatric disorder in female carriers of the fragile X chromosome. Archives of General Psychiatry, 45, 25–30.Google Scholar
Rosanoff, A. J., Handy, L. M. & Plesset, I. R. (1937) The etiology of mental deficiency with special reference to its occurrence in twins. Psychological Monograph, 216, 1–137.Google Scholar
Sanger, R., Tippett, P., Gavin, J., et al (1977) Xg groups and sex chromosome abnormalities in people of northern European ancestry: an addendum. Journal of Medical Genetics, 14, 210–213.Google Scholar
Schiff, M. & Lewontin, R. (1986) Education and Class: The Irrelevance of IQ Genetic Studies. Oxford: Clarendon Press.Google Scholar
Schwartz, C. E. (1993) Invited editorial: X linked mental retardation: In pursuit of a gene map. American Journal of Human Genetics, 52, 1025–1031.Google Scholar
Serra, A. & Neri, G. (1990) Trisomy 21: Conference Report and 1990 update. American Journal of Medical Genetics (suppl.) 7, 11–19.Google ScholarPubMed
Sherman, S. L., Jacobs, P. A., Morton, N. E., et al (1985) Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Human Genetics, 69, 289–299.Google Scholar
Stewart, D. A., Netley, C. T., & Park, E. (1982) Summary of clinical findings of children with 47XXY, 47XYY and 47XXX karyotypes. In Birth Defects: Original Article Series (ed. Stewart, D. A.), pp. 1–5. New York: Alan R. Liss, Inc.Google Scholar
Sutherland, G. R. (1977) Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science, 197, 265–266.Google Scholar
Telvi, L., LeBoyer, M., Chiron, C., et al (1991) The fragile site Xp22 in Rett syndrome as a consequence of a “chromosome breakage syndrome”. Psychiatric Genetics, 2, 57(Abstr.).Google Scholar
Theilgaard, A. (1984) A psychological study of the personalities of XYY and XXY men. Acta Psychiatrica Scandinavica (suppl. 315), 1–133.Google Scholar
Verkerk, A. J., Pieretti, M., Sutcliffe, J. S., et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakage point cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914.Google Scholar
Wahlstrom, J. (1990) Gene map of mental retardation. Journal of Mental Deficiency Research, 34, 11–27.Google Scholar
Wahlstrom, J., Gillberg, C., Gustavson, K. G., et al (1986) Infantile autism and the fragile X syndrome. A Swedish population multicenter study. American Journal of Medical Genetics, 23, 403–408.CrossRefGoogle Scholar
Walzer, S. (1985) X-chromosome abnormalities and cognitive development: implications for understanding normal human development. Journal of Child Psychology and Psychiatry, 26, 177–184.Google Scholar
Webb, T. (1991) Molecular genetics of fragile X: a cytogenetics viewpoint. Report of the Fifth International Symposium on X linked Mental Retardation, Strasbourg, France, 12–16 August 1991. Journal of Medical Genetics, 28, 814–817.Google Scholar
Webb, T. & Thake, A. (1991) Moderate and mild mental retardation in the Martin-Bell syndrome. Journal of Mental Deficiency Research, 35, 521–528.Google Scholar
Witkin, H. A., Mednick, S. A. & Schulsinger, F. (1976) Criminality in XYY and XXY men. Science, 193, 547–555.CrossRefGoogle ScholarPubMed
Wolff, P. H., Gardner, J., Lappen, J., et al (1988) Variable expression of the fragile X syndrome in heterozygote females of normal intelligence. American Journal of Medical Genetics, 30, 213–225.Google Scholar
Woo, S. L. C., Lidsky, A. S., Guttler, F., et al (1983) Cloned human phenylalanine hydroxylase gene allows prenatal detection of classical phenylketonuria. Nature, 306, 151–155.Google Scholar
Yu, S., Pritchard, M., Kremer, E., et al (1991) Fragile X genotype characterised by an unstable region of DNA. Science, 252, 1179–1181.Google Scholar
Yu, S., Mulley, J., Loesch, D., et al (1992) Fragile X syndrome: unique genetics of the heritable unstable element. American Journal of Medical Genetics, 50, 968–980.Google Scholar
Zellweger, H. & Soper, R. T. (1979) The Prader-Willi syndrome. Medical Hygiene, 37, 3338–3345.Google Scholar
Zoghbi, H. Y. (1988) Genetic aspects of Rett syndrome. Journal of Child Neurology (suppl. 3), S76–S78.Google Scholar
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