Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features

Cell Reports
Mariam AlmuriekhiMasaharu Noda

Abstract

Sotos syndrome, characterized by intellectual disability and characteristic facial features, is caused by haploinsufficiency in the NSD1 gene. We conducted an etiological study on two siblings with Sotos features without mutations in NSD1 and detected a homozygous frameshift mutation in the APC2 gene by whole-exome sequencing, which resulted in the loss of function of cytoskeletal regulation in neurons. Apc2-deficient (Apc2-/-) mice exhibited impaired learning and memory abilities along with an abnormal head shape. Endogenous Apc2 expression was downregulated by the knockdown of Nsd1, indicating that APC2 is a downstream effector of NSD1 in neurons. Nsd1 knockdown in embryonic mouse brains impaired the migration and laminar positioning of cortical neurons, as observed in Apc2-/- mice, and this defect was rescued by the forced expression of Apc2. Thus, APC2 is a crucial target of NSD1, which provides an explanation for the intellectual disability associated with Sotos syndrome.

References

May 1, 1992·Journal of Medical Genetics·T R ColeH E Hughes
Jan 1, 1994·Journal of Medical Genetics·T R Cole, H E Hughes
Feb 11, 1997·American Journal of Medical Genetics·G B SchaeferT R Cole
Apr 1, 1997·The Journal of Pathology·C A MidgleyV J Bubb
Mar 16, 2002·Nature Genetics·Naohiro KurotakiNaomichi Matsumoto
Mar 3, 2005·American Journal of Medical Genetics. Part a·M CecconiFrancesca Faravelli
Jun 9, 2005·American Journal of Human Genetics·Katrina Tatton-BrownUNKNOWN Childhood Overgrowth Collaboration
Sep 14, 2006·European Journal of Human Genetics : EJHG·Katrina Tatton-Brown, Nazneen Rahman
Jan 7, 2009·American Journal of Medical Genetics. Part a·Judith E AllansonGiovanni Neri
May 26, 2009·Nature Genetics·Xavier Hubert JaglinJamel Chelly
Sep 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Takafumi ShintaniMasaharu Noda
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·María BerdascoManel Esteller
Sep 8, 2010·Hormones and Behavior·Jun Xu, Megan Andreassi
Jan 12, 2011·Current Neurology and Neuroscience Reports·Judy S Liu
Feb 4, 2012·Journal of Human Genetics·Yuriko YonedaNaomichi Matsumoto
May 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Takafumi ShintaniMasaharu Noda
Dec 13, 2012·Journal of Medical Genetics·Donna M McDonald-McGinnLoydie A Jerome-Majewska
Apr 18, 2013·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Katrina Tatton-Brown, Nazneen Rahman
Jun 7, 2014·Annals of Pediatric Endocrinology & Metabolism·Jung Min Ko

❮ Previous
Next ❯

Citations

Mar 13, 2016·Cellular and Molecular Life Sciences : CMLS·Dieudonnée van de WilligeAnna Akhmanova
May 31, 2016·Molecular Cytogenetics·Pietro PalumboMassimo Carella
Mar 23, 2017·American Journal of Medical Genetics. Part a·Ebtesam AbdallaUlrich Zechner
Jul 1, 2017·International Journal of Molecular Sciences·Jeong-Hoon KimKyoung Sang Cho
Nov 22, 2017·American Journal of Medical Genetics. Part a·Anjana KarAshwin Dalal
Oct 10, 2019·Human Molecular Genetics·Jill A Fahrner, Hans T Bjornsson
Jan 8, 2020·Genes, Brain, and Behavior·Sabrina OishiMichael Piper
Apr 25, 2020·Frontiers in Endocrinology·Yentl HuybrechtsWim Van Hul
Jul 19, 2018·Nature Communications·Olga I KahnCasper C Hoogenraad
Apr 9, 2019·Journal of Molecular Biology·Laurence SerreIsabelle Arnal
May 26, 2021·Epilepsia Open·Olivier FortinKenneth A Myers
Oct 3, 2015·Genome Research·Hans Tomas Bjornsson
Nov 9, 2020·Seizure : the Journal of the British Epilepsy Association·Vincenzo MastrangeloBarbara Mostacci

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.