Abstract
Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficien...Continue Reading
References
Mar 15, 2006·Nature Reviews. Genetics·Ryan R BrinkmanMark E Samuels
Dec 30, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Fowzan S Alkuraya
Jan 11, 2012·Journal of Medical Genetics·Hanan E ShamseldinFowzan S Alkuraya
Apr 27, 2013·Journal of Medical Genetics·Anas M AlazamiFowzan S Alkuraya
Nov 29, 2013·Human Mutation·Nouran AdlyFowzan S Alkuraya
Dec 10, 2013·Nature Biotechnology·Zhong-Yi Wang, Hong-Yu Zhang
Sep 24, 2014·PLoS Biology·Brooke TataNicolas de Roux
Oct 22, 2014·Molecular Genetics & Genomic Medicine·Fowzan S Alkuraya
Dec 17, 2014·Trends in Genetics : TIG·Fowzan S Alkuraya
Jan 6, 2015·Cell Reports·Anas M AlazamiFowzan S Alkuraya
Jan 30, 2015·Molecular Genetics & Genomic Medicine·Kalliopi SofouJorge Asin-Cayuela
Feb 11, 2015·Molecular Psychiatry·G McMichaelA H MacLennan
Feb 14, 2015·Journal of Medical Genetics·Nisha PatelFowzan S Alkuraya
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 17, 2015·Scientific Reports·Karyn Meltz SteinbergRoger Pamphlett
Jul 27, 2015·Human Genetics·Ranad ShaheenFowzan S Alkuraya
Jul 30, 2015·Human Mutation·Nara SobreiraAda Hamosh
Dec 4, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ranad ShaheenFowzan S Alkuraya
Feb 5, 2016·American Journal of Medical Genetics. Part a·Ayman W El-HattabFowzan S Alkuraya
Apr 14, 2016·Human Genetics·Fowzan S Alkuraya
Apr 29, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Mohamed AbouelhodaFowzan S Alkuraya
Jun 13, 2016·Journal of Translational Medicine·Ewa PronickaRafał Płoski
Aug 20, 2016·American Journal of Medical Genetics. Part a·Hanan E ShamseldinFowzan S Alkuraya
Oct 7, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hanan E ShamseldinFowzan S Alkuraya
Nov 30, 2016·Genome Biology·Ranad ShaheenFowzan S Alkuraya
Jan 13, 2017·Journal of Human Genetics·Takeshi MizuguchiNaomichi Matsumoto
Jan 21, 2017·Human Mutation·Erica D SmithKelly D Farwell Hagman
Mar 23, 2017·Genome Medicine·Mohammad K EldomeryJames R Lupski
Apr 7, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Dorota MoniesFowzan S Alkuraya
May 6, 2017·American Journal of Human Genetics·Kym M BoycottHanns Lochmüller
May 30, 2017·American Journal of Human Genetics·Natasha T StrandeJonathan S Berg
May 31, 2017·Annals of Neurology·Ranad ShaheenFowzan S Alkuraya
Jun 11, 2017·Human Genetics·Dorota MoniesFowzan S Alkuraya
Aug 11, 2017·Clinical and Translational Science·Hugh J S DawkinsUNKNOWN International Rare Diseases Research Consortium (IRDiRC)
Aug 11, 2017·Clinical and Translational Science·Christopher P AustinUNKNOWN International Rare Diseases Research Consortium (IRDiRC)
Nov 3, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sophie NambotUNKNOWN Orphanomix Physicians' Group
Jan 13, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Caroline F WrightUNKNOWN DDD Study
Feb 6, 2018·Nature Reviews. Genetics·Caroline F WrightHelen V Firth
Apr 6, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sateesh MaddirevulaFowzan S Alkuraya
Citations
Jan 19, 2019·Human Genetics·Marco FicheraMaurizio Elia
Jul 25, 2019·Molecular Genetics & Genomic Medicine·Miroslava HancarovaZdenek Sedlacek
May 28, 2019·Journal of Medical Genetics·Lisa Jean EwansTony Roscioli
Sep 7, 2019·European Journal of Human Genetics : EJHG·Isabel Filges, Petter Stromme
Jan 7, 2020·American Journal of Medical Genetics. Part a·Louise Amlie-WolfMitchell Simon
Jan 9, 2020·American Journal of Medical Genetics. Part a·Laura PölslerSabine Rudnik-Schöneborn
Jun 24, 2020·American Journal of Medical Genetics. Part a·Nada Alsahan, Fowzan S Alkuraya
May 8, 2020·European Journal of Human Genetics : EJHG·Claudia Gonzaga-JaureguiJames R Lupski
May 28, 2019·American Journal of Medical Genetics. Part a·Zafer YükselEvren Gümüş
Dec 12, 2019·Frontiers in Immunology·Bin LaiXiaofeng Yang
May 3, 2019·Clinical Genetics·Katja KlothGeorg Rosenberger
Feb 15, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hanan E ShamseldinFowzan S Alkuraya
Apr 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wendy WenderskiJoseph G Gleeson
Jun 25, 2019·European Journal of Human Genetics : EJHG·Ange-Line BruelChristel Thauvin-Robinet
Apr 8, 2020·CEN Case Reports·Naoya MorisadaKazumoto Iijima
May 27, 2020·BMC Neurology·Mohammed Z SeidahmedNamik Kaya
May 21, 2020·Disease Models & Mechanisms·Rebecca YarwoodMartin Lowe
Jul 19, 2020·BMC Medical Genomics·Ahmed AlfaresMajid Alfadhel
Aug 31, 2019·Scientific Reports·Pauline E SchneebergerKerstin Kutsche
Sep 25, 2020·Experimental Dermatology·Antti M Salo, Johanna Myllyharju
Nov 4, 2020·Journal of Neuroscience Research·Lucie Y AhnHelen C Miranda
Jan 8, 2021·Kidney International·Qi LiAlda Tufro
Jan 19, 2021·Frontiers in Genetics·Sateesh MaddirevulaFowzan S Alkuraya
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yuko FukataMasaki Fukata
Dec 29, 2020·European Journal of Medical Genetics·Chisei SatohKoh-Ichiro Yoshiura
Mar 1, 2021·Journal of Human Genetics·Sachiko NishinaNoriyuki Azuma
Apr 25, 2021·Kidney International·Johannes S Schlöndorff
Feb 26, 2021·Clinical Genetics·Maian RoifmanDavid Chitayat
May 9, 2021·Human Genome Variation·Jong Seop KimTae-Joon Cho
May 12, 2021·Human Genetics·Andreas R JaneckeRoger Janz
May 18, 2021·Journal of Pediatric Genetics·Tibor KalmárLászló Sztriha
Jun 6, 2021·Neuropharmacology·Yuko FukataMasaki Fukata
Jun 18, 2021·Molecular Genetics & Genomic Medicine·Kholoud N Al-ShafaiXavier Estivill
Aug 29, 2021·Pharmaceuticals·Marcin JanowskiAleksandra Pękowska
Sep 30, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Nobuhiko OkamotoKenjiro Kosaki
Oct 15, 2021·Genome Medicine·Hanan E ShamseldinFowzan S Alkuraya