The Pathophysiological Link Between Reelin and Autism: Overview and New Insights

Marcello Scala; Eleonora A Grasso; Giuseppe Di Cara; Antonella Riva; Pasquale Striano; Alberto Verrotti

doi:10.3389/fgene.2022.869002

The Pathophysiological Link Between Reelin and Autism: Overview and New Insights

Front Genet. 2022 Mar 29:13:869002. doi: 10.3389/fgene.2022.869002. eCollection 2022.

Authors

Marcello Scala^{1

2}, Eleonora A Grasso³, Giuseppe Di Cara⁴, Antonella Riva^{1

2}, Pasquale Striano^{1

2}, Alberto Verrotti⁴

Affiliations

¹ Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal, and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
² Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, University of Genoa, Genoa, Italy.
³ Department of Paediatrics, University of Chieti, Chieti, Italy.
⁴ Department of Medicine and Surgery, Pediatric Clinic, University of Perugia, Perugia, Italy.

Abstract

Reelin is a secreted extracellular matrix protein playing pivotal roles in neuronal migration and cortical stratification during embryonal brain development. In the adult brain, its activity is crucial for synaptic plasticity, memory processing, and cognition. Genetic alterations in RELN have been variably reported as possible contributors to the pathogenesis of autism spectrum disorders (ASD). In particular, GCCs repeats in the 5'UTR, and single nucleotide polymorphysms (SNPs) in RELN have been suggested to affect brain development and predispose to autism. We reviewed pertinent literature on RELN expression and haplotypes transmission in children with ASD, critically analyzing available evidence in support of the pathophysiological association between Reelin deficiency and ASD.

Keywords: ASD; GGC repeats; RELN; autism; brain development; reelin; single nucleotide polymorphisms.

Publication types

Review