Vestibular phenotype-genotype correlation in a cohort of 90 patients with Usher syndrome.
Usher syndrome
atypical Usher syndrome
balance
novel variants
vestibular
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
22
04
2020
revised:
14
10
2020
accepted:
18
10
2020
pubmed:
23
10
2020
medline:
24
11
2021
entrez:
22
10
2020
Statut:
ppublish
Résumé
Usher syndrome has been historically categorized into one of three classical types based on the patient phenotype. However, the vestibular phenotype does not infallibly predict which Usher genes are mutated. Conversely, the Usher syndrome genotype is not sufficient to reliably predict vestibular function. Here we present a characterization of the vestibular phenotype of 90 patients with clinical presentation of Usher syndrome (59 females), aged 10.9 to 75.5 years, with genetic variants in eight Usher syndromic genes and expand the description of atypical Usher syndrome. We identified unexpected horizontal semicircular canal reactivity in response to caloric and rotational stimuli in 12.5% (3 of 24) and 41.7% (10 of 24), respectively, of our USH1 cohort. These findings are not consistent with the classical phenotypic definition of vestibular areflexia in USH1. Similarly, 17% (6 of 35) of our cohort with USH2A mutations had saccular dysfunction as evidenced by absent cervical vestibular evoked myogenic potentials in contradiction to the classical assumption of normal vestibular function. The surprising lack of consistent genotypic to vestibular phenotypic findings as well as no clear vestibular phenotypic patterns among atypical USH cases, indicate that even rigorous vestibular phenotyping data will not reliably differentiate the three USH types.
Identifiants
pubmed: 33089500
doi: 10.1111/cge.13868
pmc: PMC7821283
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
226-235Informations de copyright
© 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
Références
Am J Med Genet. 2001 Jun 15;101(2):181-3
pubmed: 11391666
Orphanet J Rare Dis. 2013 Aug 08;8:122
pubmed: 23924366
Otol Neurotol. 2015 Aug;36(7):1238-44
pubmed: 26111076
Ophthalmic Genet. 2020 Oct;41(5):401-412
pubmed: 32372680
J Med Genet. 2002 Apr;39(4):281-3
pubmed: 11950859
Br J Ophthalmol. 1997 Jan;81(1):46-53
pubmed: 9135408
Am J Hum Genet. 1999 Apr;64(4):1221-5
pubmed: 10090909
Clin Genet. 2018 Apr;93(4):812-821
pubmed: 29112224
Laryngoscope. 1989 Jan;99(1):66-72
pubmed: 2562904
Annu Rev Genomics Hum Genet. 2001;2:271-97
pubmed: 11701652
Mol Vis. 2010 Sep 30;16:1898-906
pubmed: 21031134
Adv Otorhinolaryngol. 2011;70:56-65
pubmed: 21358186
Am J Hum Genet. 1998 Sep;63(3):909-12
pubmed: 9718356
Hum Genet. 2016 Apr;135(4):441-450
pubmed: 26969326
Exp Eye Res. 2000 Aug;71(2):173-81
pubmed: 10930322
Clin Genet. 2005 Sep;68(3):204-14
pubmed: 16098008
Orphanet J Rare Dis. 2011 Oct 17;6:65
pubmed: 22004887
Auris Nasus Larynx. 2016 Apr;43(2):149-54
pubmed: 26254957
Otolaryngol Head Neck Surg. 2017 Nov;157(5):853-860
pubmed: 28653555
J Med Genet. 2006 Sep;43(9):763-8
pubmed: 16679490
Otol Neurotol. 2015 Sep;36(8):1421-7
pubmed: 26192261
J Med Genet. 2011 Nov;48(11):767-75
pubmed: 21940737
Am J Med Genet. 1994 Mar 1;50(1):32-8
pubmed: 8160750
Otol Neurotol. 2013 Apr;34(3):484-9
pubmed: 23442567
Am J Med Genet A. 2015 Dec;167A(12):2957-65
pubmed: 26416264
JAMA Ophthalmol. 2015 Feb;133(2):157-64
pubmed: 25375654
Genet Med. 2010 Aug;12(8):512-6
pubmed: 20613545
Arch Phys Med Rehabil. 2006 Mar;87(3):402-7
pubmed: 16500176
Am J Hum Genet. 2002 Aug;71(2):262-75
pubmed: 12075507
Front Neurol. 2019 Aug 08;10:830
pubmed: 31440199
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Int J Pediatr Otorhinolaryngol. 2012 Sep;76(9):1292-6
pubmed: 22721527
Otol Neurotol. 2016 Jun;37(5):608
pubmed: 27093031
Genet Med. 2019 Oct;21(10):2239-2247
pubmed: 30894701
BMC Ophthalmol. 2017 Aug 24;17(1):157
pubmed: 28838317
Int J Audiol. 2005 May;44(5):307-16
pubmed: 16028794
J Mol Med (Berl). 2005 Dec;83(12):1025-32
pubmed: 16283141
Clin Genet. 2021 Feb;99(2):226-235
pubmed: 33089500
J Hum Genet. 2010 Jun;55(6):327-35
pubmed: 20379205
Clin Genet. 2004 Dec;66(6):525-9
pubmed: 15521980
Clin Genet. 2010 Dec;78(6):601-3
pubmed: 21044053
Mol Ther Methods Clin Dev. 2019 Nov 27;17:156-173
pubmed: 31909088
Am J Hum Genet. 2001 Jan;68(1):26-37
pubmed: 11090341