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Human Genetics

, Volume 100, Issue 2, pp 224–229 | Cite as

Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients

  • S. M. Klauck
  • Ewald Münstermann
  • Bettina Bieber-Martig
  • Dorothea Rühl
  • Sonja Lisch
  • Gabriele Schmötzer
  • Annemarie Poustka
  • Fritz Poustka
Original investigation

Abstract

A genetic etiology in autism is now strongly supported by family and twin studies. A 3:1 ratio of affected males to females suggests the involvement of at least one X-linked locus in the disease. Several reports have indicated an association of the fragile X chromosomal anomaly at Xq27.3 (FRAXA) with autism, whereas others have not supported this finding. We have so far collected blood from 105 simplex and 18 multiplex families and have assessed 141 patients by using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Scale, and psychometric tests. All four ADI-R algorithm criteria were met by 131 patients (93%), whereas 10 patients (7%) showed a broader phenotype of autism. Southern blot analysis was performed with three different enzymes, and filters were hybridized to an FMR-1-specific probe to detect amplification of the CCG repeat at FRAXA, to the complete FMR-1 cDNA probe, and to additional probes from the neighborhood of the gene. No significant changes were found in 139 patients (99%) from 122 families, other than the normal variations in the population. In the case of one multiplex familiy with three children showing no dysmorphic features of the fragile X syndrome (one male meeting 3 out of 4 ADI-algorithm criteria, one normal male with slight learning disability but negative ADI-R testing, and one fully autistic female), the FRAXA full-mutation-specific CCG-repeat expansion in the genotype was not correlated with the autism phenotype. Further analysis revealed a mosaic pattern of methylation at the FMR-1 gene locus in the two sons of the family, indicating at least a partly functional gene. Therefore, we conclude that the association of autism with fragile X at Xq27.3 is non-existent and exclude this location as a candidate gene region for autism.

Keywords

Learning Disability Molecular Genetic Analysis Dysmorphic Feature Mosaic Pattern Autism Diagnostic Observation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • S. M. Klauck
    • 1
  • Ewald Münstermann
    • 1
  • Bettina Bieber-Martig
    • 2
  • Dorothea Rühl
    • 2
  • Sonja Lisch
    • 2
  • Gabriele Schmötzer
    • 2
  • Annemarie Poustka
    • 1
  • Fritz Poustka
    • 2
  1. 1.Deutsches Krebsforschungszentrum, Molekulare Genomanalyse, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany Tel.: +49-6221-424745; Fax: +49-6221-423454DE
  2. 2.Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Johann-Wolfgang-Goethe-Universität Frankfurt, Deutschordenstrasse 50, D-60590 Frankfurt am Main, GermanyDE

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