Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Kevin T BoothShelley D Smith

Abstract

The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family. Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family. Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 gene within the DFNA37 locus. Genotyping of all 48 family members confirmed segregation of this variant with the deafness phenotype in the extended family. The c.652-2A>C variant is novel, highly conserved, and confirmed in vitro to alter RNA splicing. We have identified COL11A1 as the gene responsible for deafness at the DFNA37 locus. Previously, COL11A1 was solely associated with Marshall and Stickler syndromes. This study expands its phenotypic spectrum to include nonsyndromic deafness. The implications of this discovery are val...Continue Reading

References

Oct 1, 1995·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·D R KeeneN P Morris
Nov 3, 1998·Pediatric Radiology·J Spranger
Dec 2, 1999·Nature Genetics·W T McGuirtR J Smith
Jul 11, 2000·Archives of Otolaryngology--head & Neck Surgery·A J GriffithP R Kileny
Apr 20, 2001·Annals of Medicine·J Myllyharju, K I Kivirikko
Jun 18, 2002·Journal of Structural Biology·David J S Hulmes
Mar 17, 2004·Osteoarthritis and Cartilage·R R RodriguezL C Bridgewater
Sep 11, 2004·International Journal of Audiology·Niels Christian Stenklev, Einar Laukli
Nov 26, 2004·The Annals of Otology, Rhinology, and Laryngology·Els M R De LeenheerCor W R J Cremers
Sep 10, 2005·American Journal of Medical Genetics. Part a·Peter S RoseClair A Francomano
Oct 26, 2006·The Journal of Biological Chemistry·Lisa R WarnerJulia Thom Oxford
Dec 1, 2006·Journal of the Association for Research in Otolaryngology : JARO·Rutger F PlantingaArjan J Bosman
Sep 18, 2008·Current Opinion in Otolaryngology & Head and Neck Surgery·Guy P RichardsonIan J Russell
May 28, 2009·Nature Neuroscience·Christine Petit, Guy P Richardson
Aug 27, 2010·Clinical Genetics·L RigoliC Di Bella
Nov 3, 2010·American Journal of Human Genetics·Stuart W TompsonDaniel H Cohn
Nov 16, 2010·Annual Review of Physiology·Guy P RichardsonChristine Petit
Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·Sylvie Ricard-Blum
Jun 18, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hutton M KearneyUNKNOWN Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee
Nov 1, 2012·Orphanet Journal of Rare Diseases·Frederic R E AckeEls M R De Leenheer
Apr 15, 2014·Human Mutation·Hela AzaiezRichard J H Smith
Apr 8, 2015·Molecular and Cellular Probes·Barbara VonaThomas Haaf
Jan 21, 2016·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Frederic R AckeEls M R De Leenheer
Dec 22, 2017·Human Mutation·Kevin T BoothRichard J Smith

❮ Previous
Next ❯

Citations

Jan 3, 2019·Genomics & Informatics·Nathanial T Carpena, Min Young Lee
Apr 4, 2020·The Laryngoscope·Shadi AhmadmehrabiDaniel J Rader
May 20, 2020·Annals of Human Genetics·Jana ČopíkováRadka Kremlíková Pourová
Sep 25, 2020·JAMA Otolaryngology-- Head & Neck Surgery·Royce E CliffordCaroline M Nievergelt
Dec 12, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Zohreh Talebizadeh
Nov 28, 2021·European Journal of Human Genetics : EJHG·Adebolajo AdeyemoIsabelle Roux

❮ Previous
Next ❯

Methods Mentioned

BETA
chip
exome sequencing
electrophoresis
genetic modifications

Software Mentioned

NNSPLICE
Burrows Aligner ( BWA
Merlin
Human Splicing Finder
dbNSFP
SAMtools

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.