Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region.
The higher prevalence of autism in males than in females suggests the possible involvement of the X chromosome. To test the hypothesis that there are mutations increasing susceptibility to autism on the X chromosome, and in particular the distal portion of the long arm that encompasses the FMRI and MECP2 loci, a genetic linkage study was performed. Twenty-two fragile X-negative families multiplex for autism and related disorders were used for the study. Linkage analysis, for markers in the Xq27-q28 region, using model-free likelihood-based analysis, produced a maximum MLOD of 1.7 for the narrowest diagnostic category of the typical autism/severe autism spectrum, and nonparametric analysis produced a maximum non-parametric lod (NPL) score of 2.1 for a broad phenotype diagnostic model. Thus, this study offers modest support for a susceptibility locus for autism within the Xq27-q28 region. Further genetic investigations of this region are warranted.
Vincent
John B
JB
Molecular Psychiatry Laboratory, Department of Psychiatry and Behavioural Sciences, Windeyer Institute of Medical Science, University College London, London. john_vincent@camh.net
Melmer
Georg
G
Bolton
Patrick F
PF
Hodgkinson
Steve
S
Holmes
Debbie
D
Curtis
David
D
Gurling
Hugh M D
HM
D001321:Autistic Disorder / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D020022:Genetic Predisposition to Disease; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D018709:Statistics, Nonparametric
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C497683:FMR1 protein, human; C497392:MECP2 protein, human