Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network.
A recent study by Persico et al. [2001: Mol Psychiatry 6:150-159] suggests alleles of a CGG polymorphism, just 5' of the reelin gene (RELN) initiator codon, confer liability for autism, especially alleles bearing 11 or more CGG repeats (long alleles). The association is consistent across both a case-control and family-based sample. We attempted to replicate their finding using a larger, independent family-based sample from the NIH Collaborative Programs of Excellence in Autism (CPEA) Network. In our data, allele transmissions to individuals with autism versus unaffected individuals are unbiased, both when alleles are classified by repeat length and when they are classified into long/short categories. Because of the apparent linkage of autism to chromosome 7q, particularly related to the development of language, we also evaluate the relationship between Reelin alleles and the age at which autism subjects use their first word or first phrase. Neither is significantly associated with Reelin alleles. Our results are not consistent with a major role for Reelin alleles in liability to autism.
Devlin
Bernie
B
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bennett
Pamela
P
Dawson
Geraldine
G
Figlewicz
Denise A
DA
Grigorenko
Elena L
EL
McMahon
William
W
Minshew
Nancy
N
Pauls
David
D
Smith
Moyra
M
Spence
M Anne
MA
Rodier
Patricia M
PM
Stodgell
Chris
C
Schellenberg
Gerard D
GD
D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D018911:Trinucleotide Repeats / Q000235:genetics*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases