Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder

A M Persico; L D'Agruma; N Maiorano; A Totaro; R Militerni; C Bravaccio; T H Wassink; C Schneider; R Melmed; S Trillo; F Montecchi; M Palermo; T Pascucci; S Puglisi-Allegra; K L Reichelt; M Conciatori; R Marino; C C Quattrocchi; A Baldi; L Zelante; P Gasparini; F Keller; Collaborative Linkage Study of Autism

doi:10.1038/sj.mp.4000850

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Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder

Journal article

Peer reviewed

Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder

A M Persico, L D'Agruma, N Maiorano, A Totaro, R Militerni, C Bravaccio, T H Wassink, C Schneider, R Melmed, S Trillo, …

Molecular psychiatry, Vol.6(2), pp.150-159

03/2001

DOI: 10.1038/sj.mp.4000850

PMID: 11317216

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Abstract

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.

Haplotypes

Trinucleotide Repeats

Serotonin - physiology

Exons

Humans

Middle Aged

Family Health

Male

Case-Control Studies

Aged, 80 and over

Adult

Female

Serine Endopeptidases

Brain Chemistry - genetics

Autistic Disorder - genetics

Genetic Predisposition to Disease

RNA Splice Sites - genetics

Extracellular Matrix Proteins - genetics

Risk Factors

Nerve Tissue Proteins

Genetic Markers

Autistic Disorder - epidemiology

Cell Adhesion Molecules, Neuronal - genetics

Linkage Disequilibrium

Point Mutation

Skull - anatomy & histology

Alleles

Aged

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder
Creators: A M Persico - Laboratory of Neuroscience, Department of Physiology and Neuroscience, Libera Università Campus Bio-Medico, Via Longoni 83, I-00155 Rome, Italy
L D'Agruma
N Maiorano
A Totaro
R Militerni
C Bravaccio
T H Wassink
C Schneider
R Melmed
S Trillo
F Montecchi
M Palermo
T Pascucci
S Puglisi-Allegra
K L Reichelt
M Conciatori
R Marino
C C Quattrocchi
A Baldi
L Zelante
P Gasparini
F Keller
Collaborative Linkage Study of Autism
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.6(2), pp.150-159
DOI: 10.1038/sj.mp.4000850
PMID: 11317216
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Publisher: England
Grant note: E.0858 / Telethon TGM06S01 / Telethon
Language: English
Date published: 03/2001
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003985102771

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