Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability.

American Journal of Human Genetics
Annabel WhibleyF Lucy Raymond

Abstract

Copy number variants and indels in 251 families with evidence of X-linked intellectual disability (XLID) were investigated by array comparative genomic hybridization on a high-density oligonucleotide X chromosome array platform. We identified pathogenic copy number variants in 10% of families, with mutations ranging from 2 kb to 11 Mb in size. The challenge of assessing causality was facilitated by prior knowledge of XLID-associated genes and the ability to test for cosegregation of variants with disease through extended pedigrees. Fine-scale analysis of rare variants in XLID families leads us to propose four additional genes, PTCHD1, WDR13, FAAH2, and GSPT2, as candidates for XLID causation and the identification of further deletions and duplications affecting X chromosome genes but without apparent disease consequences. Breakpoints of pathogenic variants were characterized to provide insight into the underlying mutational mechanisms and indicated a predominance of mitotic rather than meiotic events. By effectively bridging the gap between karyotype-level investigations and X chromosome exon resequencing, this study informs discussion of alternative mutational mechanisms, such as noncoding variants and non-X-linked disease, wh...Continue Reading

Citations

Dec 12, 2012·Molecular Biology and Evolution·Melissa A Wilson Sayres, Kateryna D Makova
Jun 15, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Gary StobbeFuki M Hisama
Jul 31, 2013·Human Mutation·Joep de LigtJayne Y Hehir-Kwa
Jan 25, 2014·American Journal of Medical Genetics. Part a·Francisco MartínezCarmen Orellana
Mar 19, 2015·European Journal of Human Genetics : EJHG·Bàrbara TorricoClaudio Toma
Sep 12, 2015·American Journal of Medical Genetics. Part a·Sulman BasitKhushnooda Ramzan
Jun 11, 2015·European Journal of Human Genetics : EJHG·Ching MoeyCheryl Shoubridge
Sep 4, 2015·Genome Biology·Christelle Robert, Mick Watson
Feb 2, 2017·Human Genome Variation·Nobuhiko OkamotoIssei Imoto
Mar 29, 2011·BMC Medical Genetics·Mohammad M Ghahramani SenoStephen W Scherer
May 20, 2011·Human Genetics·Philip M BooneJames R Lupski
Oct 12, 2014·Human Molecular Genetics·Mariana Ramos-BrossierPierre Billuart
Apr 18, 2015·Orphanet Journal of Rare Diseases·Sandra SirrsMartin Kaczocha
Mar 24, 2016·Nature·Michael F WellsMichael M Halassa
Apr 30, 2016·F1000Research·Pietro Chiurazzi, Filomena Pirozzi
Jan 6, 2018·Molecular Psychiatry·Hao HuHossein Najmabadi
Dec 5, 2017·Journal of the International Neuropsychological Society : JINS·Deborah Fein, Molly Helt
Aug 31, 2012·Clinical Genetics·A RiessA Tzschach
Apr 17, 2014·Molecular Genetics and Genomics : MGG·Jianqiu XiaoFeng Zhang
May 20, 2011·American Journal of Medical Genetics. Part a·Philip D PallisterJohn M Opitz
Jan 24, 2015·Journal of Medical Genetics·Mark A CorbettMichael Field
Oct 16, 2012·Development and Psychopathology·Michael Gill
Nov 12, 2014·Human Mutation·Anneke T Vulto-van SilfhoutArjan P M de Brouwer
Apr 4, 2017·American Journal of Medical Genetics. Part a·Anna PodolskaNataliya Di Donato
Mar 23, 2017·Genome Medicine·Mohammad K EldomeryJames R Lupski
Sep 25, 2017·Genome Medicine·Tomasz GambinPaweł Stankiewicz
Jan 28, 2018·European Journal of Human Genetics : EJHG·Annemieke J M H VerkerkBen A Oostra
Apr 28, 2020·Neural Development·Andrew C Giles, Brock Grill
Sep 27, 2014·American Journal of Medical Genetics. Part a·Naiara Braz da RochaJuliana Forte Mazzeu
Apr 12, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Marsha D Speevak, Sandra A Farrell
Oct 17, 2013·Human Mutation·Ying QiaoEvica Rajcan-Separovic
Dec 5, 2012·American Journal of Medical Genetics. Part a·Yuri A ZarateRoger E Stevenson
Nov 16, 2010·Nature Genetics·Lisenka E L M VissersJoris A Veltman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

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.

Autism: Treatment Targets

The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.