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J Med Genet. 1995 April; 32(4): 269–274.
PMCID: PMC1050373

Association study with two markers of a human homeogene in infantile autism.


Epidemiological data and family studies in autism show that there is a genetic susceptibility factor in the aetiology of this syndrome. We carried out an association study in infantile autism. Two markers of the homeogene EN2 involved in cerebellar development were tested in a population of 100 autistic children and in a population of 100 control children. With the MP4 probe showing a PvuII polymorphism, significant differences in the allele frequencies between the two populations were found (chi 2 = 7.99, df = 1, p < 0.01). With the MP5 probe showing an SstI polymorphism, no difference appeared (chi 2 = 1.17, not significant). Several clinical examinations allowed us to characterise the autistic children. Most of them had high scores for autistic behaviour and language disorders but low scores for neurological syndromes. Two children had a significant family history and six children had confirmed syndromes or diseases of genetic origin. Discriminant analysis between clinical and molecular data did not give significant results. These preliminary results must be supported by further analyses of this gene and by studies of its potential involvement in the pathophysiology of the autistic syndrome.

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  • Ornitz EM, Ritvo ER. Neurophysiologic mechanisms underlying perceptual inconstancy in autistic and schizophrenic children. Arch Gen Psychiatry. 1968 Jul;19(1):22–27. [PubMed]
  • Ornitz EM. Neurophysiology of infantile autism. J Am Acad Child Psychiatry. 1985 May;24(3):251–262. [PubMed]
  • Tanguay PE, Edwards RM, Buchwald J, Schwafel J, Allen V. Auditory brainstem evoked responses in autistic children. Arch Gen Psychiatry. 1982 Feb;39(2):174–180. [PubMed]
  • Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988 May 26;318(21):1349–1354. [PubMed]
  • DeLong GR, Bean SC, Brown FR., 3rd Acquired reversible autistic syndrome in acute encephalopathic illness in children. Arch Neurol. 1981 Mar;38(3):191–194. [PubMed]
  • Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985 Jun;35(6):866–874. [PubMed]
  • Courchesne E, Lincoln AJ, Yeung-Courchesne R, Elmasian R, Grillon C. Pathophysiologic findings in nonretarded autism and receptive developmental language disorder. J Autism Dev Disord. 1989 Mar;19(1):1–17. [PubMed]
  • Rumsey JM, Hamburger SD. Neuropsychological findings in high-functioning men with infantile autism, residual state. J Clin Exp Neuropsychol. 1988 Mar;10(2):201–221. [PubMed]
  • Leaton RN, Supple WF., Jr Cerebellar vermis: essential for long-term habituation of the acoustic startle response. Science. 1986 Apr 25;232(4749):513–515. [PubMed]
  • Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985 Jun;35(6):866–874. [PubMed]
  • Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry. 1986 Jul;143(7):862–866. [PubMed]
  • Bauman ML. Microscopic neuroanatomic abnormalities in autism. Pediatrics. 1991 May;87(5 Pt 2):791–796. [PubMed]
  • Ritvo ER, Jorde LB, Mason-Brothers A, Freeman BJ, Pingree C, Jones MB, McMahon WM, Petersen PB, Jenson WR, Mo A. The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. Am J Psychiatry. 1989 Aug;146(8):1032–1036. [PubMed]
  • August GJ, Stewart MA, Tsai L. The incidence of cognitive disabilities in the siblings of autistic children. Br J Psychiatry. 1981 May;138:416–422. [PubMed]
  • Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry. 1977 Sep;18(4):297–321. [PubMed]
  • Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM. Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry. 1985 Jan;142(1):74–77. [PubMed]
  • Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405–416. [PubMed]
  • Hérault J, Perrot A, Barthélémy C, Büchler M, Cherpi C, Leboyer M, Sauvage D, Lelord G, Mallet J, Müh JP. Possible association of c-Harvey-Ras-1 (HRAS-1) marker with autism. Psychiatry Res. 1993 Mar;46(3):261–267. [PubMed]
  • Le Roux I, Joliot AH, Bloch-Gallego E, Prochiantz A, Volovitch M. Neurotrophic activity of the Antennapedia homeodomain depends on its specific DNA-binding properties. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9120–9124. [PubMed]
  • Davis CA, Joyner AL. Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development. Genes Dev. 1988 Dec;2(12B):1736–1744. [PubMed]
  • Davis CA, Noble-Topham SE, Rossant J, Joyner AL. Expression of the homeo box-containing gene En-2 delineates a specific region of the developing mouse brain. Genes Dev. 1988 Mar;2(3):361–371. [PubMed]
  • Joyner AL, Herrup K, Auerbach BA, Davis CA, Rossant J. Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. Science. 1991 Mar 8;251(4998):1239–1243. [PubMed]
  • Köhler A, Logan C, Joyner AL, Muenke M. Regional assignment of the human homeobox-containing gene EN1 to chromosome 2q13-q21. Genomics. 1993 Jan;15(1):233–235. [PubMed]
  • Logan C, Joyner AL. An SstI RFLP for the human homeo box-containing gene EN2. Nucleic Acids Res. 1989 Apr 11;17(7):2878–2878. [PMC free article] [PubMed]
  • Logan C, Joyner AL. PvuII and RsaI RFLPs for the human homeo box-containing gene EN2. Nucleic Acids Res. 1989 Apr 11;17(7):2879–2879. [PMC free article] [PubMed]
  • Garreau B, Bruneau N, Martineau J. Autisme et psychoses de l'enfant. Signes neurologiques et examens complémentaires. Soins Psychiatr. 1987 Aug-Sep;(82-83):15–17. [PubMed]
  • Garreau B, Barthelemy C, Sauvage D, Leddet I, LeLord G. A comparison of autistic syndromes with and without associated neurological problems. J Autism Dev Disord. 1984 Mar;14(1):105–111. [PubMed]
  • Lelord G, Muh JP, Barthelemy C, Martineau J, Garreau B, Callaway E. Effects of pyridoxine and magnesium on autistic symptoms--initial observations. J Autism Dev Disord. 1981 Jun;11(2):219–230. [PubMed]
  • Barthelemy C, Adrien JL, Tanguay P, Garreau B, Fermanian J, Roux S, Sauvage D, Lelord G. The Behavioral Summarized Evaluation: validity and reliability of a scale for the assessment of autistic behaviors. J Autism Dev Disord. 1990 Jun;20(2):189–204. [PubMed]
  • Adrien JL, Lenoir P, Martineau J, Perrot A, Hameury L, Larmande C, Sauvage D. Blind ratings of early symptoms of autism based upon family home movies. J Am Acad Child Adolesc Psychiatry. 1993 May;32(3):617–626. [PubMed]
  • Gillberg C, Wahlström J. Chromosome abnormalities in infantile autism and other childhood psychoses: a population study of 66 cases. Dev Med Child Neurol. 1985 Jun;27(3):293–304. [PubMed]
  • Einfeld S, Molony H, Hall W. Autism is not associated with the fragile X syndrome. Am J Med Genet. 1989 Oct;34(2):187–193. [PubMed]
  • Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol. 1983 Oct;14(4):471–479. [PubMed]
  • Olsson B, Rett A. Behavioral observations concerning differential diagnosis between the Rett syndrome and autism. Brain Dev. 1985;7(3):281–289. [PubMed]
  • Folstein SE, Piven J. Etiology of autism: genetic influences. Pediatrics. 1991 May;87(5 Pt 2):767–773. [PubMed]
  • Hier DB, LeMay M, Rosenberger PB. Autism and unfavorable left-right asymmetries of the brain. J Autism Dev Disord. 1979 Jun;9(2):153–159. [PubMed]
  • Damasio H, Maurer RG, Damasio AR, Chui HC. Computerized tomographic scan findings in patients with autistic behavior. Arch Neurol. 1980 Aug;37(8):504–510. [PubMed]
  • Rumsey JM, Duara R, Grady C, Rapoport JL, Margolin RA, Rapoport SI, Cutler NR. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography. Arch Gen Psychiatry. 1985 May;42(5):448–455. [PubMed]
  • Zilbovicius M, Garreau B, Tzourio N, Mazoyer B, Bruck B, Martinot JL, Raynaud C, Samson Y, Syrota A, Lelord G. Regional cerebral blood flow in childhood autism: a SPECT study. Am J Psychiatry. 1992 Jul;149(7):924–930. [PubMed]

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