Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function

Human Mutation
Saima RiazuddinThomas B Friedman

Abstract

Recessive mutations of MYO7A, encoding unconventional myosin VIIA, can cause either a deaf-blindness syndrome (type 1 Usher syndrome; USH1B) or nonsyndromic deafness (DFNB2). In our study, deafness segregating as a recessive trait in 24 consanguineous families showed linkage to markers for the DFNB2/USH1B locus on chromosome 11q13.5. A total of 23 of these families segregate USH1 due to 17 homozygous mutant MYO7A alleles, of which 14 are novel. One family segregated nonsyndromic hearing loss DFNB2 due to a novel three-nucleotide deletion in an exon of MYO7A (p.E1716del) encoding a region of the tail domain. We hypothesized that DFNB2 alleles of MYO7A have residual myosin VIIA. To address this question we investigated the effects of several mutant alleles by making green fluorescent protein (GFP) tagged cDNA expression constructs containing engineered mutations of mouse Myo7a at codons equivalent to pathogenic USH1B and DFNB2 alleles of human MYO7A. We show that in transfected mouse hair cells an USH1B mutant GFP-myosin VIIa does not localize properly to inner ear hair cell stereocilia. However, a GFP-myosin VIIa protein engineered to have an equivalent DFNB2 mutation to p.E1716del localizes correctly in transfected mouse hair c...Continue Reading

References

Mar 1, 1994·American Journal of Medical Genetics·R J SmithL Tranebjaerg
Jan 1, 1997·The British Journal of Ophthalmology·C I HopeA R Fielder
Jun 16, 1997·The Journal of Cell Biology·T HassonD P Corey
Jun 3, 2000·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·K C Holmes, M A Geeves
Nov 4, 2000·American Journal of Human Genetics·L M AstutoW J Kimberling
Jun 8, 2001·American Journal of Medical Genetics·Z B ZinaC Petit
Jun 9, 2001·American Journal of Human Genetics·Z M AhmedE R Wilcox
Aug 7, 2001·Human Molecular Genetics·K N AlagramamG S Hagemen
Nov 10, 2001·Annual Review of Genomics and Human Genetics·C Petit
May 7, 2002·American Journal of Medical Genetics·Lisa M AstutoWilliam J Kimberling
Jun 6, 2003·Clinical Genetics·Z M AhmedE R Wilcox
Mar 26, 2004·Nature Reviews. Molecular Cell Biology·Lynne E Maquat
Oct 1, 2004·Documenta Ophthalmologica. Advances in Ophthalmology·Michael F MarmorUNKNOWN International Society for Clinical Electrophysiology of Vision
Dec 14, 2004·Human Molecular Genetics·Avital AdatoChristine Petit
Feb 17, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mathias SenftenUlrich Müller
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yi YangJames R Sellers
Jul 14, 2006·Nature·Kavitha ThirumuruganPeter J Knight
Jan 4, 2007·The Journal of Cell Biology·T Lynne BlasiusKristen J Verhey

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Citations

Feb 7, 2009·Journal of Human Genetics·Xiao Mei OuyangXue Zhong Liu
Jun 22, 2012·Journal of Human Genetics·Thomas J JaworekZubair M Ahmed
Jan 8, 2011·The Journal of Biological Chemistry·Jessica HaithcockEva Forgacs
Jul 9, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·William J KimberlingRichard J H Smith
Dec 3, 2011·Journal of Medical Genetics·Polona Le Quesne StabejMaria Bitner-Glindzicz
May 17, 2011·Orphanet Journal of Rare Diseases·Crystel BonnetFrançoise Denoyelle
Dec 20, 2012·PloS One·Kerry A MillerShehnaaz S M Manji
Dec 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Martin SchwanderUlrich Müller
Jun 2, 2012·Frontiers in Bioscience (Landmark Edition)·Duygu Duman, Mustafa Tekin
Jan 11, 2013·Genetics Research International·Joel Sng, Thomas Lufkin
Nov 19, 2014·Orphanet Journal of Rare Diseases·María J AparisiJosé M Millán
Feb 13, 2016·Ophthalmic Genetics·Horbelys O GuzmánRené A Utrera
Dec 15, 2012·International Journal of Pediatric Otorhinolaryngology·Hidekane YoshimuraShin-ichi Usami
Dec 28, 2011·Hearing Research·Meghan C DrummondThomas B Friedman
Aug 31, 2011·Journal of Molecular Biology·Rebecca J MoenMargaret A Titus
May 29, 2008·Clinical Genetics·Z M AhmedT B Friedman
Dec 24, 2010·Annals of the New York Academy of Sciences·Dorith RavivKaren B Avraham
Feb 6, 2010·Clinical Genetics·M S HildebrandR J H Smith
Jan 7, 2010·Human Mutation·Sandie Le Guédard-MéreuzeSylvie Tuffery-Giraud
Jul 18, 2015·Genetic Testing and Molecular Biomarkers·Denise YanXue Zhong Liu
Nov 26, 2008·Biochimica Et Biophysica Acta·Cristina ZadroMassimo Carella
Dec 8, 2014·Biochimica Et Biophysica Acta·Pranav Mathur, Jun Yang
Oct 17, 2015·Clinical Otolaryngology : Official Journal of ENT-UK ; Official Journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery·A M M OonkR J E Pennings
Oct 13, 2016·International Journal of Pediatric Otorhinolaryngology·Ling ZongHongyan Jiang
Mar 28, 2017·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Charles L AnzaloneMatthew L Carlson
Jul 1, 2017·Nature Communications·I-Mei YuAnne Houdusse
Jun 19, 2013·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Mohsin ShahzadZubair M Ahmed
Mar 25, 2018·Journal of Medical Genetics·Zubair M AhmedSaima Riazuddin
Dec 11, 2014·European Journal of Human Genetics : EJHG·Atteeq U RehmanSuzanne M Leal
Nov 7, 2013·Molecular Biology Reports·Salma Ben-SalemLihadh Al-Gazali
Oct 1, 2020·Therapeutic Advances in Ophthalmology·Maria TomsMariya Moosajee
Jul 19, 2020·Scientific Reports·Memoona RamzanSadaf Naz

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