Abstract
The relationship between the fragile X syndrome (FXS) and autism is reviewed. Shortly after the FXS was first described, it was noted that certain behaviors commonly found in afflicted individuals resemble certain features of autism. Research concerning a possible relationship between these conditions is summarized. The outcome of this research indicates that FXS is not a common cause of autism, although the number of individuals with FXS who meet diagnostic criteria for autism is higher than can be accounted for by chance. The major focus of this paper highlights that FXS is a well-defined neurogenetic disease that includes a cognitive behavioral phenotype, and has both a known biological cause and an increasing well-delineated pathogenesis. Autism is a behaviorally defined syndrome whose syndromic boundaries and biological causes are not known. These profound differences complicate comparisons and causal discussions. However, the behavioral neurogenetic information available about FXS suggests certain pathways for future research directed at elucidating the syndrome of autism.
Similar content being viewed by others
REFERENCES
Abitbol, M., Menini, C., Delezoide, A. L., Rhyner, T., Vekemans, M., & Mallet, J. (1993). Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nature Genetics, 4, 147–153.
Abrams, M. T., & Reiss, A. L. (1995). The neurobiology of fragile X syndrome. Mental Retardation and Developmental Disabilities Research Reviews, 1, 269–275.
Abrams, M. T., Reiss, A. L., Freund, L. S., Baumgardner, T. L., Chase, G. A., & Denckla, M. B. (1994). Molecular-neurobehavioral associations in females with the fragile X full mutation. American Journal of Medical Genetics, 51, 317–327.
American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed., Rev.). Washington, DC: Author.
Arnold, A. P. (1996). Genetically triggered sexual differentiation of brain and behavior. Hormones and Behavior, 30, 495–505.
August, G. J., & Lockhart, L. H. (1984). Familial autism and the fragile X chromosome. Journal of Autism and Developmental Disorders, 14, 197–204.
Bailey, D. B. J., & Nelson D. (1995). The nature and consequences of fragile X syndrome. Mental Retardation and Developmental Disabilities Research Reviews, 1, 238–244.
Bauman, M. L., & Kemper, T. L. (1994). Neuroanatomic observations of the brain in autism. The neurobiology of autism (pp. 119–145). Baltimore: Johns Hopkins University Press.
Baumgardner, T. L., Green, K. E., & Reiss, A. L. (1994). A behavioral neurogenetics approach to developmental disabilities: Gene-brain-behavior associations. Current Opinions in Neurology, 7, 172–178.
Baumgardner, T., Reiss, A. L., Freund, L., & Abrams, M. (1995). Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics, 95, 744–752.
Borghgraef, M., Fryns, J. P., Dielkens, A., Pyck, K., & Van den Berghe, H. (1987). Fragile (X) syndrome: a study of the psychological profile in 23 prepubertal patients. Clinical Genetics, 32, 179–186.
Brainard, S. S., Schreiner, R. A., & Hagerman, R. J. (1991). Cognitive profiles of the carrier fragile X woman. American Journal of Medical Genetics, 38, 505–508.
Bregman, J. D. (1991). Current developments in the understanding of mental retardation. Part II: Psychopathology. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 861–872.
Bregman, J. D., Dykens, E., Watson, M., Ort, S. I., & Leckman, J. F. (1987). Fragile X syndrome: variability of phenotypic expression. Journal of the American Academy of Child and Adolescent Psychiatry, 26, 463–471.
Bregman, J. D., Leckman, J. F., & Ort, S. I. (1988). Fragile X syndrome: Genetic predisposition to psychopathology. Journal of Autism and Developmental Disorders, 18, 343–354.
Brown, C. J., Carrel, L., & Willard, H., F. (1997). Expression of Genes from the Human Active and Inactive X Chromosomes. American Journal of Human Genetics, 60, 1333–1343.
Brown, W. T., Houck, G. J. r., Jeziorowska, A., Levinson, F. N., Ding, X., Dobkin, C., Zhong, N., Henderson, J., Brooks, S. S., & Jenkins, E. C. (1993). Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. Journal of American Medical Association, 270, 1569–1575.
Cohen, I. L., Fisch, G. S., Sudhalter, V., Wolf-Schein, E. G., Hanson, D., Hagerman, R., Jenkins, E. C., & Brown, W. T. (1988). Social gaze, social avoidance, and repetitive behavior in fragile X males: a controlled study. American Journal on Mental Retardation, 92, 436–446.
Cohen, I. L., Sudhalter, V., Pfadt, A., Jenkins, E. C., Brown, W. T., & Vietze, P. M. (1991a). Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues. American Journal of Human Genetics, 48, 195–202.
Cohen, I. L., Sudhalter, V., Pfadt, A., Jenkins, E. C., Brown, W. T., & Vietze, P. M. (1991b). Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues. American Journal of Human Genetics, 48, 195–202.
Courchesne, E., Saitoh, O., Yeung-Courchesne, R., Press, G. A., Lincoln, A. J., Haas, R. H., & Schreibman, L. (1994). Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: Identification of hyplastic and hyperplastic subgroups with MR Imaging. American Journal of Roentgenology, 162, 123–130.
Crowe, S. F., & Hay, D. A. (1990). Neuropsychological dimensions of the fragile X syndrome: support for a non-dominant hemisphere dysfunction hypothesis. Neuropsychologia, 28, 9–16.
de Vries, B. B., & Niermeijer, M. F. (1994). The Prader-Willi-like phenotype in fragile X patients: a designation facilitating clinical (and molecular) differential diagnosis [letter]. Journal of Medical Genetics, 31.
Devys, D., Lutz, Y., Rouyer, N., Bellocq, J. P., & Mandel, J. L. (1993). The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nature Genetics, 4, 335–340.
Disteche, C., C. (1997). The Great Escape. American Journal of Human Genetics, 60, 1312–1315.
Dykens, E. M. (1995). Adaptive Behavior in Males With fragile X Syndrome. Mental retardation and developmental disabilities, 1, 281–285.
Dykens, E. M., Hodapp, R. M., & Leckman, J. F. (1989). Adaptive and maladaptive functioning of institutionalized and noninstitutionalized fragile X males. Journal of the American Academy of Child and Adolescent Psychiatry, 28, 427–430.
Dykens, E. M., Hodapp, R. M., Ort, S. I., & Leckman, J. F. (1993). Trajectory of adaptive behavior in males with fragile X syndrome. Journal of Autism and Developmental Disorders, 23, 135–145.
Dykens, E. M., & Volkmar, F. R. (1997). Medical conditions associated with autism. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 388–410). New York: Wiley.
Eichler, E. E., Richards, S., Gibbs, R. A., & Nelson, D. L. (1994). Fine structure of the human FMR1 gene. Human Molecular Genetics, 3, 684–685.
Einfeld, S., Molony, H., & Hall, W. (1989). Autism is not associated with the fragile X syndrome. American Journal of Medical Genetics, 34, 187–193.
Einfeld, S. L., Tonge, B. J., & Florio, T. (1994a). Behavioral and emotional disturbance in fragile X syndrome. American Journal of Medical Genetics, 51, 386–391.
Einfeld, S. L., Tonge, B. J., & Florio, T. (1994b). Behavioral and emotional disturbance in fragile X syndrome. American Journal of Medical Genetics, 51, 386–391.
Feng, Y., Gutekunst, C.-A., Eberhart, D. E., Yi, H., Warren, S. T., & Hersch, S. M. (1997). Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. Journal of Neuroscience, 17, 1539–1547.
Fisch, G. S. (1993). What is associated with the fragile X syndrome? American Journal of Medical Genetics, 48, 112–121.
Fisch, G. S., Holden, J. J., Simensen, R., Carpenter, N., Howard-Peebles, P. N., Maddalena, A., Sandgrund, A., Jacques, J. R., & McGann, B. (1994). Is fragile X syndrome a pervasive developmental disability? Cognitive ability and adaptive behavior in males with the full mutation. American Journal of Medical Genetics, 51, 346–352.
Fisch, G. S., Simensen, R., Arinami, T., Borghgraef, M., & Fryns, J. P. (1994). Longitudinal changes in IQ among fragile X females: A preliminary multicenter analysis. American Journal of Medical Genetics, 51, 353–357.
Freund, L. S., Baumgardner, T., Mazzocco, M. M., Denckla, M. B., & Reiss, A. L. (in press). The influence of X chromosome genes on neurobehavioral function in females: Fragile X and Turner syndromes. Development and Psychopathology.
Freund, L. S., & Reiss, A. L. (1991). Cognitive profiles associated with the fra(X) syndrome in males and females. American Journal of Medical Genetics, 38, 542–547.
Freund, L. S., Reiss, A. L., & Abrams, M. T. (1993). Psychiatric disorders associated with fragile X in the young female. Pediatrics, 91, 321–329.
Freund, L., Reiss, A., Baumgardner, T., & Denckla, M. (in press). Social information processing in girls with fragile X or Turner syndrome. Development and Psychopathology.
Fryns, J. P. (1984). The fragile X syndrome. A study of 83 families. Clinical Genetics, 26, 497–528.
Fu, Y. H., Kuhl, D. P., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkerk, A. J., Holden, J. J., Fenwick, R. G., 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, 1047–1058.
Gillberg, C. (1995). Specific Syndromes not Otherwise Referred to. In G. Christopher (Ed.), Clinical Child Neuropsychiatry (pp. 185–267). Cambridge, U.K.: Cambridge University Press.
Gillberg, C., Persson, E., & Wahlstrom, J. (1986). The autism-fragile-X syndrome (AFRAX): A population-based study of ten boys. Journal of Mental Deficiency Research, 30, 27–39.
Graves, J. A. (1995). The origin and function of the mammalian Y chromosome and Y-borne genes: An evolving understanding. Bioessays, 17, 311–320.
Hagerman, R. J. (1991). Physical and behavioral phenotype. In R. J. Hagerman & A. C. Cronister (Eds.), Fragile X syndrome (pp. 3–68). Baltimore: Johns Hopkins University Press.
Hagerman, R. J. (1995). Molecular and clinical correlations in fragile X syndrome. Mental Retardation and Developmental Disabilities Research Review, 1, 276–280.
Hagerman, R. J., & Cronister, A. J. (Eds.). (1991). Epidemiology, Fragile X Syndrome (2nd ed.). Baltimore: Johns Hopkins University Press.
Hagerman, R. J., Hull, C. E., Safanda, J. F., Carpenter, I., Staley, L. W., O'Connor, R. A., Seydel, C., Mazzocco, M. M., Snow, K., Thibodeau, S. N., et al. (1994). High functioning fragile X males: Demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. American Journal of Medical Genetics, 51, 298–308.
Hallmayer, J., Hebert, J. M., Spiker, D., Lotspeich, L., McMahon, W. M., Petersen, P. B., Nicholas, P., Pingree, C., Lin, A. A., Cavalli-Sforza, L. L., Risch, N., & Ciaranello, R. (1996). Autism and the X chromosome. Archives of General Psychiatry, 53, 985–989.
Hanzlik, A. J., Osemlak, H. M., Hauser, M. A., & Kurnit, D. M. (1993). A recombination-based assay demonstrates that the fragile X sequence is transcribed widely during development. Nature Genetic, 3, 44–48.
Heitz, D., Devys, D., Imbert, G., Kretz, C., & Mandel, J. L. (1992). Inheritance of the fragile X syndrome: Size of the fragile X premutation is a major determinant of the transition to full mutation. Journal of Medical Genetics, 29, 794–801.
Henn, W., & Zang, K. D. (1997). Mosaicism in Turner's Syndrome. Nature, 390, 569.
Hinds, H. L., Ashley, C. T., Sutcliffe, J. S., Nelson, D. L., Warren, S. T., Housman, D. E., & Schalling, M. (1993). Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nature Genetics, 3, 36–43.
Hinton, V. J., Brown, W. T., Wisniewski, K., & Rudelli, R. D. (1991). Analysis of neocortex in three males with the fragile X syndrome. American Journal of Medical Genetics, 41, 289–294.
Hornstra, I. K., Nelson, D. L., Warren, S. T., & Yang, T. P. (1993). High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome. Human Molecular Genetics, 2, 1659–1665.
Jenkins, E. C., Brown, W. T., Brooks, J., Duncan, C. J., Rudelli, R. D., & Wisniewski, H. M. (1984). Experience with prenatal fragile X detection. American Journal of Medical Genetics, 17, 215–239.
Jensen, P. S., Mrazek, D., Knapp, P. K., Steinberg, L., Pfeffer, C., Schowalter, J., & Shapiro, T. (1997). Evolution and revolution in child psychiatry: ADHD as a disorder of adaptation. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1672–1681.
Kaufman, W. E., & Reiss, A. L. (in press). Molecular and cellular genetics of fragile X syndrome. American Journal of Medical Genetics.
Kemper, M. B., Hagerman, R. J., Ahmad, R. S., & Mariner, R. (1986). Cognitive profiles and the spectrum of clinical manifestations in heterozygous fra (X) females. American Journal of Medical Genetics, 23, 139–156.
Khandjian, E. W., Fortin, A., Thibodeau, A., Tremblay, S., Cote, F., Devys, D., Mandel, J. L., & Rousseau, F. (1995). A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture. Human Molecular Genetics, 4, 783–789.
Lachiewicz, A. M., Gullion, C. M., Spiridigliozzi, G. A., & Aylsworth, A. S. (1987). Declining IQs of young males with the fragile X syndrome. American Journal of Mental Retardation, 92, 272–278.
Lahn, B. T., & Page, D. C. (1997). Functional Coherence of the Y Chromosome. Science, 278, 675–680.
Leckman, J. F. (1997). Discussion of evolution and revolution in child psychiatry: ADHD as a disorder of adaptation. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1680–1681.
Lubs, H. A. (1969). A marker X-chromosome. American Journal of Human Genetics, 21, 231–244.
Lyford, G. L., Yamagata, K., Kaufmann, W. E., Barnes, C. A., Sanders, L. K., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lanahan, A. A., & Worley, P. F. (1995). Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron, 13, 433–445.
Mazzocco, M. M., Hagerman, R. J., & Pennington, B. F. (1992). Problem solving limitations among cytogenetically expressing fragile X women. American Journal of Medical Genetics, 43, 78–86.
Mazzocco, M. M., Kates, W. R., Baumgardner, T. L., Freund, L. S., & Reiss, A. L. (1997). Autistic behaviors among girls with fragile X syndrome. Journal Autism and Developmental Disorders, 27, 415–435.
Mazzocco, M. M., Pennington, B. F., & Hagerman, R. J. (1993). The neurocognitive phenotype of female carriers of fragile X: Additional evidence for specificity. Journal of Developmental and Behavioral Pediatrics, 14, 328–335.
Mazzocco, M. M., Pennington, B. F., & Hagerman, R. J. (1994). Social cognition skills among females with fragile X. Journal of Autism and Developmental Disorders, 24, 473–485.
Meryash, D. L., Szymanski, L. S., & Gerald, P. S. (1982). Infantile autism associated with the fragile-X syndrome. Journal of Autism and Developmental Disorders, 12, 295–301.
Minshew, N. J., Sweeney, J. A., & Bauman, M., L. (1997). Neurological Aspects of autism. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 344–369). New York: Wiley.
Nelson, D. L., & Warren, S. T. (1993). Trinucleotide repeat instability: When and where? (news; published erratum appears in Nature Genetics, 4, 217) Nature Genetics, 4, 107–108.
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boue, J., Bertheas, M. F., & Mandel, J. L. (1991). Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science, 252, 1097–1102.
Pennington, B. F., Schreiner, R. A., & Sudhalter, V. (1991). Towards a neuropsychology of fragile X syndrome. In S. Hagerman (Ed.), The fragile X syndrome (pp. 173–201) city: publisher.
Pieretti, M., Zhang, F. P., Fu, Y. H., Warren, S. T., Oostra, B. A., Caskey, C. T., & Nelson, D. L. (1991). Absence of expression of the FMR-1 gene in fragile X syndrome. Cell, 66, 817–822.
Piven, J., Wzorek, M., Landa, R., Lainhart, J., Bolton, P., Chase, G. A., & Folstein, S. (1994). Personality characteristics of the parents of autistic individuals. Psychological Medicine, 24, 783–795.
Reiss, A. L. (1988). Cerebellar hypoplasia and autism. New England Journal of Medicine, 319, 1152–1153.
Reiss, A. L. (1996). Behavioral neurogenetics: Genetic conditions as models for understanding brain development, cognition, and behavior in children. Paper presented at the Models for Advancing Research on Developmental Plasticity: Integrating the Behavioral Science and the Neuroscience of Mental Health, Chantilly, VA.
Reiss, A. L., Abrams, M. T., Greenlaw, R., Freund, L., & Deckla, M. B. (1995a). Neurodevelopmental effects of the FMR-1 full mutation in humans. Nature Medicine, 1, 159–167.
Reiss, A. L., Abrams, M. T., Greenlaw, R., Freund, L., & Denckla, M. B. (1995b). Neurodevelopmental effects of X monosomy: A volumetric imaging study. Nature Medicine, 1, 159–167.
Reiss, A. L., Aylward, E., Freund, L. S., Joshi, P. K., & Bryan, R. N. (1991a). Neuroanatomy of fragile X syndrome: The posterior fossa. Annals of Neurology, 29, 26–32.
Reiss, A. L., & Freund, L. (1990). Fragile X syndrome, DSM-III-R, and autism. Journal of the American Academy of Child and Adolescent Psychiatry, 29, 885–891.
Reiss, A. L., & Freund, L. (1992). Behavioral phenotype of fragile X syndrome: DSM-III-R autistic behavior in male children. American Journal of Medical Genetics, 43, 35–46.
Reiss, A. L., Freund, L., Abrams, M. T., Boehm, C., & Kazazian, H. (1993). Neurobehavioral effects of the fragile X premutation in adult women: A controlled study. American Journal of Human Genetics, 52, 884–894.
Reiss, A. L., Freund, L. F., Baumgardner, T. L., Abrams, M. T., & Denckla, M. B. (1995). Contribution of the FMR1 gene mutation to human intellectual dysfunction. Nature Genetics, 11, 331–334.
Reiss, A. L., Freund, L., Tseng, J. E., & Joshi, P. K. (1991). Neuroanatomy in fragile X females: The posterior fossa. American Journal of Human Genetics, 49, 279–288.
Reiss, A. L., Lee, J., & Freund, L. (1994). Neuroanatomy of fragile X syndrome: The temporal lobe. Neurology, 44, 1317–1324.
Rousseau, F., Heitz, D., Biancalana, V., Blumenfeld, S., Kretz, C., Boue, J., Tommerup, N., Van Der Hagen, C., DeLozier-Blanchet, C., Croquette, M. F., Gilgenkrantz, S., Jalbert, P., Voelckel, M. A., Oberlé, I., & Mandel, J. L. (1991). Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. New England Journal of Medicine, 325, 1673–1681.
Rousseau, F., Heitz, D., Tarleton, J., MacPherson, J., Malmgren, H., Dahl, N., Barnicoat, A., Mathew, C., Mornet, E., Tejada, I., Maddalena, A., Spiegel, R., Schinzel, A., Marcos, J. A. G., Schwartz, C., & Mandel, J. L. (1994). A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: The first 2,253 cases. American Journal of Human Genetics, 55, 225–237.
Rudelli, R. D., Brown, W. T., Wisniewski, K., Jenkins, E. C., Laure, K. M., Connell, F., & Wisniewski, H. M. (1985). Adult fragile X syndrome. Clinico-neuropathologic findings. Acta Neuropathology (Berlin), 67, 289–295.
Rutter, M., Bailey, A., Simonoff, E., & Pickles, A. (1997). Genetic Influences and Autism. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 370–387). New York: Wiley.
Schafer, A. J., & Goodfellow, P. N. (1996). Sex determination in humans. Bioessays, 18(12), 955–963.
Schapiro, M. B., Murphy, D. G., Hagerman, R. J., Azari, N. P., Alexander, G. E., Miezejeski, C. M., Hinton, V. J., Horwitz, B., Haxby, J. V., Kumar, A., et al. (1995). Adult fragile X syndrome: Neuropsychology, brain anatomy, and metabolism. American Journal of Medical Genetics, 60, 480–493.
Skuse, D. H., James, R. S., Bishop, D. V. M., Coppin, B., Dalton, P., Aamodt-Leeper, G., Bacarese-Hamilton, M., Cresswell, C., McGurk, R., & Jacobs, P. A. (1997). Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function. Nature, 387, 705–708.
Snow, K., Doud, L. K., Hagerman, R., Pergolizzi, R. G., Erster, S. H., & Thibodeau, S. N. (1993). Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population. American Journal of Human Genetics, 53, 1217–1228.
Steward, O. (1995). The process of reinnervation in the dentate gyrus of adult rats: Gene expression by neurons during the period of lesion-induced growth. Journal of Comparative Neurology, 359, 391–411.
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992). DNA methylation represses FMR-1 transcription in fragile X syndrome. Human Molecular Genetics, 1, 397–400.
Sutherland, G. R. (1977). Fragile sites on human chromosomes: Demonstration of their dependence on the type of tissue culture medium. Science, 197, 265–266.
Theobald, T. M., Hay, D. A., & Judge, C. (1987). Individual variation and specific cognitive deficits in the fra(X) syndrome. American Journal of Medical Genetics, 28, 1–11.
Verheij, C., Bakker, C. E., de Graaff, E., Keulemans, J., Willemsen, R., Verkerk, A. J., Galjaard, H., Reuser, A. J., Hoogeveen, A. T., & Oostra, B. A. (1993). Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature, 363, 722–724.
Verkerk, A. J., de Graaff, E., De Boulle, K., Eichler, E. E., Konecki, D. S., Reyniers, E., Manca, A., Poustka, A., Willems, P. J., Nelson, D. L., et al. (1993). Alternative splicing in the fragile X gene FMR1. Human Molecular Genetics, 2, 399–404.
Verkerk, A. J., Pieretti, M., Sutcliffe, J. S., Fu, Y. H., Kuhl, D. P., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Fuping Zhang, M. F. V., Eussen, B. E., van Ommen, G. J. B., Blonden, L. A. J., Riggins, G. J., Chastain, J. L., Kunst, C. B., Galjaard, H., Caskey, C. T., Nelson, D. L., Oostra, B. A., & Warren, S. T. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914.
Volkmar, F. R., Klin, A., & Cohen, D. J. (1997). Diagnosis and Classification of Autism and Related Conditions: Consensus and Issues. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 5–40). New York: Wiley.
Wing, L. (1997). Syndromes of autism and atypical development. In D. J. Cohen & F. R. Volkmar (Eds.), Handbook of autism and pervasive developmental disorders (2nd ed., pp. 148–172). New York: Wiley.
World Health Organization. (1992). The ICD-10 classification of mental and behavioral disorders: Clinical descriptions and diagnostic guidelines. Geneva: Author.
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, 1179–1181.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Feinstein, C., Reiss, A.L. Autism: The Point of View from Fragile X Studies. J Autism Dev Disord 28, 393–405 (1998). https://doi.org/10.1023/A:1026000404855
Issue Date:
DOI: https://doi.org/10.1023/A:1026000404855