Clinical exome sequencing reveals locus heterogeneity and phenotypic variability of cohesinopathies.

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Bo YuanPengfei Liu

Abstract

Defects in the cohesin pathway are associated with cohesinopathies, notably Cornelia de Lange syndrome (CdLS). We aimed to delineate pathogenic variants in known and candidate cohesinopathy genes from a clinical exome perspective. We retrospectively studied patients referred for clinical exome sequencing (CES, N = 10,698). Patients with causative variants in novel or recently described cohesinopathy genes were enrolled for phenotypic characterization. Pathogenic or likely pathogenic single-nucleotide and insertion/deletion variants (SNVs/indels) were identified in established disease genes including NIPBL (N = 5), SMC1A (N = 14), SMC3 (N = 4), RAD21 (N = 2), and HDAC8 (N = 8). The phenotypes in this genetically defined cohort skew towards the mild end of CdLS spectrum as compared with phenotype-driven cohorts. Candidate or recently reported cohesinopathy genes were supported by de novo SNVs/indels in STAG1 (N = 3), STAG2 (N = 5), PDS5A (N = 1), and WAPL (N = 1), and one inherited SNV in PDS5A. We also identified copy-number deletions affecting STAG1 (two de novo, one of unknown inheritance) and STAG2 (one of unknown inheritance). Patients with STAG1 and STAG2 variants presented with overlapping features yet without characterist...Continue Reading

References

Apr 11, 2006·Nature Genetics·Antonio MusioLidia Larizza
May 18, 2007·American Journal of Medical Genetics. Part a·Antonie D KlineAngelo Selicorni
Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eric D RubioAnton Krumm
Apr 7, 2009·American Journal of Human Genetics·Helen V FirthNigel P Carter
Sep 19, 2009·American Journal of Medical Genetics. Part a·Alasdair G W HunterIan D Krantz
Oct 2, 2009·Clinical Genetics·J Liu, I D Krantz
Aug 20, 2010·Nature·Michael H KageyRichard A Young
Mar 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Gero StrübbeRenato Paro
Aug 20, 2011·Science·David A SolomonTodd Waldman
Jan 14, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Davut PehlivanJames R Lupski
May 29, 2012·American Journal of Human Genetics·Matthew A DeardorffFrank J Kaiser
Aug 14, 2012·Nature·Matthew A DeardorffKatsuhiko Shirahige
Dec 21, 2012·Journal of Applied Genetics·Alina KuzniackaJanusz Limon
Sep 17, 2013·Human Mutation·Linda ManniniAntonio Musio
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Oct 15, 2013·Nature Genetics·David A SolomonTodd Waldman
Nov 5, 2013·The EMBO Journal·Sevil SofuevaSuzana Hadjur
May 24, 2014·Nature Reviews. Cancer·Ana Losada
Oct 19, 2014·JAMA : the Journal of the American Medical Association·Yaping YangChristine M Eng
Jan 13, 2015·The Journal of Clinical Investigation·Bo YuanJames R Lupski
Feb 19, 2015·Nature Reviews. Molecular Cell Biology·Benjamin L Allen, Dylan J Taatjes
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Sep 20, 2015·European Journal of Medical Genetics·Jessica H R GoldsteinJirair K Bedoyan
Dec 8, 2015·American Journal of Human Genetics·Jason A O'RaweGholson J Lyon
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Dec 14, 2016·The New England Journal of Medicine·Jennifer E PoseyJames R Lupski
Jan 26, 2017·Journal of Medical Genetics·Daphné LehalleLaurence Faivre
Mar 16, 2017·American Journal of Medical Genetics. Part a·Sureni V MullegamaJulian A Martinez-Agosto
Sep 25, 2017·Genome Medicine·Tomasz GambinPaweł Stankiewicz
Dec 22, 2017·NPJ Genomic Medicine·Fernanda C SoardiSérgio D J Pena

❮ Previous
Next ❯

Citations

Feb 26, 2019·American Journal of Medical Genetics. Part a·Victoria F WagnerLaura S Farach
Jan 19, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jennifer E PoseyUNKNOWN Centers for Mendelian Genomics
Jul 25, 2019·Brain : a Journal of Neurology·Paul KruszkaMaximilian Muenke
Nov 7, 2019·American Journal of Medical Genetics. Part a·Eyby LeonRoser Urreizti
Mar 4, 2020·American Journal of Medical Genetics. Part a·Morasha Plesser DuvdevaniTamar Harel
Jul 23, 2020·Brain : a Journal of Neurology·Himanshu Goel, Gayathri Parasivam
Sep 14, 2019·Cell Cycle·Jessica PichéGregor Andelfinger
Dec 15, 2019·International Journal of Molecular Sciences·Emanuele MicaglioCarlo Pappone
Oct 6, 2020·Human Genome Variation·Hiromi AoiNaomichi Matsumoto
Mar 21, 2020·Human Genetics·Lianne C KrabRaoul C Hennekam
Jul 25, 2019·Journal of Human Genetics·Hiromi AoiNaomichi Matsumoto
Sep 22, 2020·Expert Review of Molecular Diagnostics·James R LupskiJennifer E Posey
Jun 10, 2020·Nature Reviews. Cancer·Todd Waldman
Jan 10, 2021·Human Genome Variation·Hiromi AoiNaomichi Matsumoto
Dec 15, 2020·Journal of Structural Biology·Jeremy D OskoDavid W Christianson
Jun 23, 2021·Blood·Johann-Christoph Jann, Zuzana Tothova
Aug 29, 2021·Pharmaceuticals·Marcin JanowskiAleksandra Pękowska
Nov 23, 2021·Frontiers in Neuroscience·Ilaria Parenti, Frank J Kaiser
Dec 16, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Chun-An ChenBo Yuan
Feb 4, 2022·Critical Reviews in Biochemistry and Molecular Biology·Wenya HouHuiqiang Lou

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing

Software Mentioned

MaxEntScan
COSMIC
ClinVar
DECIPHER
SpliceSiteFinder

Related Concepts

Related Feeds

Autism

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 on autism.