RELN Mutations in Autism Spectrum Disorder

Frontiers in Cellular Neuroscience
Dawn B Lammert, B W Howell


RELN encodes a large, secreted glycoprotein integral to proper neuronal positioning during development and regulation of synaptic function postnatally. Rare, homozygous, null mutations lead to lissencephaly with cerebellar hypoplasia (LCH), accompanied by developmental delay and epilepsy. Until recently, little was known about the frequency or consequences of heterozygous mutations. Several lines of evidence from multiple studies now implicate heterozygous mutations in RELN in autism spectrum disorders (ASD). RELN maps to the AUTS1 locus on 7q22, and at this time over 40 distinct mutations have been identified that would alter the protein sequence, four of which are de novo. The RELN mutations that are most clearly consequential are those that are predicted to inactivate the signaling function of the encoded protein and those that fall in a highly conserved RXR motif found at the core of the 16 Reelin subrepeats. Despite the growing evidence of RELN dysfunction in ASD, it appears that these mutations in isolation are insufficient and that secondary genetic or environmental factors are likely required for a diagnosis.


Mar 16, 2017·Journal of Lipid Research·Courtney Lane-Donovan, Joachim Herz
Jul 4, 2018·Human Mutation·Sandra M Sánchez-SánchezAndrea L Sertié
Aug 18, 2018·Molecular Pharmacology·Diana LupuJoëlle Rüegg
Aug 10, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Guang Yang, Alex Shcheglovitov
Nov 24, 2019·Journal of Neuroscience Research·Wei Li, Lucas Pozzo-Miller
Apr 30, 2017·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Roberto KellerMaurizio Elia
Feb 1, 2020·European Journal of Human Genetics : EJHG·Masoud GarshasbiAhmadreza Jamshidi
Apr 16, 2020·Frontiers in Psychiatry·Inmaculada Cuchillo-IbáñezJavier Sáez-Valero
Apr 5, 2020·Journal of Clinical Medicine·Sang Hoon YoonJeong Tae Do
Jul 20, 2018·Translational Psychiatry·Yuko AriokaNorio Ozaki


Apr 1, 1994·Protein Science : a Publication of the Protein Society·C L BordersV B Pett
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·C PesoldH J Caruncho
Mar 25, 1999·Genes & Development·B W HowellJonathan A Cooper
Nov 26, 1999·Neuron·G D'ArcangeloT Curran
Dec 1, 1996·Journal of Neurogenetics·N Hadj-SahraouiJ Mariani
Apr 24, 2001·Molecular Psychiatry·A M PersicoCollaborative Linkage Study of Autism
Jun 8, 2001·Human Molecular Genetics·International Molecular Genetic Study of Autism Consortium (IMGSAC)
Aug 2, 2001·American Journal of Human Genetics·International Molecular Genetic Study of Autism Consortium (IMGSAC)
Jan 30, 2002·Journal of Autism and Developmental Disorders·S Hossein FatemiG R Realmuto
Aug 9, 2002·The Journal of Biological Chemistry·Edwin J WeeberJoachim Herz
Aug 23, 2002·Molecular Psychiatry·M O KrebsParis Autism Research International Sibpair (PARIS) Study
Oct 26, 2002·Molecular Psychiatry·H ZhangJ J A Holden
Jan 16, 2003·Current Biology : CB·Lionel ArnaudJonathan A Cooper
Jan 16, 2003·Current Biology : CB·Hans H Bock, Joachim Herz
Apr 25, 2003·Cell and Tissue Research·Philippe AbsilMarcel Eens
Jun 5, 2003·Nature Reviews. Neuroscience·Fadel Tissir, André M Goffinet
Sep 30, 2003·Molecular Psychiatry·E BonoraInternational Molecular Genetic Study of Autism (IMGSAC)
Jul 24, 2004·American Journal of Human Genetics·Benjamin M Neale, Pak C Sham
Nov 5, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gundela MeyerDaniel Caput
Feb 4, 2005·Journal of Medical Genetics·J A LambInternational Molecular Genetic Study of Autism Consortium (IMGSAC)
Apr 12, 2005·Biological Psychiatry·S Hossein FatemiDavid A Pearce
Sep 9, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ying ChenJoachim Herz
Dec 13, 2005·Trends in Neurosciences·Camin Dean, Thomas Dresbach
Sep 8, 2006·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Bernard S ChangChristopher A Walsh
Sep 19, 2006·Brain Research·Roger PanteriFlavio Keller
Jun 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Norihisa YasuiJunichi Takagi
Sep 13, 2007·Molecular Psychiatry·S S Moy, J J Nadler
Sep 21, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Laurent GrocPascale Chavis
May 12, 2009·PloS One·Cecilia Gonzalez CampoPascale Chavis
Jul 15, 2009·Neurobiology of Disease·Filippo BiamonteFlavio Keller
Aug 15, 2009·Neuron Glia Biology·Mélanie SinagraPascale Chavis
Mar 13, 2010·Structure·Norihisa YasuiJunichi Takagi
Jun 19, 2010·Nature Reviews. Neuroscience·Jill L SilvermanJacqueline N Crawley
Mar 2, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Judith H Miles
Aug 16, 2011·Trends in Cell Biology·Andreas M GrabruckerTobias M Boeckers
Sep 6, 2011·Trends in Molecular Medicine·Peter B Crino

Related Concepts

Cerebellar Diseases
Conserved Sequence
Regulation of Biological Process
Isolation Aspects
RELN gene
Synaptic Transmission

Related Feeds


Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research.

Related Papers

Autism : the International Journal of Research and Practice
Dermot Bowler
Autism : the International Journal of Research and Practice
Sven Bölte
The Journal of the South Carolina Medical Association
Laura A Carpenter, Michelle M Macias
© 2020 Meta ULC. All rights reserved