Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
16
12
2019
revised:
28
01
2020
accepted:
06
02
2020
pubmed:
11
3
2020
medline:
13
4
2021
entrez:
11
3
2020
Statut:
ppublish
Résumé
To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in a national referral center. We designed two iterations of a comprehensive targeted gene panel for neuromuscular disorders. Version 1 included 336 genes, which was increased to 464 genes in Version 2. Both panels used TargetSeq Six hundred and sixty-five patients received a genetic diagnosis (30%). Diagnosed patients were significantly younger that undiagnosed patients (26.4 and 32.5 years, respectively; P = 4.6326E-9). The diagnostic success varied markedly between disease categories. Pathogenic variants in 10 genes explained 38% of the disease burden. Unexpected phenotypic expansions were discovered in multiple cases. Triage of unsolved cases for research exome testing led to the discovery of six new disease genes. A comprehensive targeted diagnostic panel was an effective method for neuromuscular disease diagnosis within the context of an Australasian referral center. Use of smaller disease-specific panels would have precluded diagnosis in many patients and increased cost. Analysis through a centralized laboratory facilitated detection of recurrent, but under-recognized pathogenic variants.
Identifiants
pubmed: 32153140
doi: 10.1002/acn3.51002
pmc: PMC7086001
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-362Informations de copyright
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
Références
J Neuromuscul Dis. 2018;5(3):307-314
pubmed: 30040739
Am J Hum Genet. 2015 Jun 4;96(6):955-61
pubmed: 26004201
Am J Hum Genet. 2016 Sep 1;99(3):666-673
pubmed: 27523598
Brain. 2012 Oct;135(Pt 10):2994-3004
pubmed: 22964162
Neuromuscul Disord. 2017 Jul;27(7):607-615
pubmed: 28554554
Nat Genet. 1993 Jul;4(3):314-20
pubmed: 8358442
Ann Neurol. 2018 Jun;83(6):1105-1124
pubmed: 29691892
Brain. 2011 Jan;134(Pt 1):171-182
pubmed: 21186264
Nat Rev Genet. 2011 May;12(5):363-76
pubmed: 21358748
Am J Hum Genet. 2018 Mar 1;102(3):505-514
pubmed: 29499166
Clin Genet. 2018 Jan;93(1):78-83
pubmed: 28378410
Genet Med. 2018 Sep;20(9):1045-1053
pubmed: 29095814
Genome Res. 2009 Sep;19(9):1527-41
pubmed: 19546169
J Neurol. 2013 May;260(5):1286-94
pubmed: 23269439
Mol Genet Genomic Med. 2014 Nov;2(6):522-9
pubmed: 25614874
Neuromuscul Disord. 2016 Aug;26(8):504-10
pubmed: 27312022
Neuromuscul Disord. 2011 Dec;21(12):833-61
pubmed: 22250299
Neurol Genet. 2018 Feb 01;4(1):e212
pubmed: 29417091
JAMA Neurol. 2018 Oct 1;75(10):1234-1245
pubmed: 29913018
J Med Genet. 1997 Jun;34(6):470-5
pubmed: 9192266
Neurol Neuroimmunol Neuroinflamm. 2018 Dec 12;6(1):e523
pubmed: 30588482
Methods Mol Biol. 2011;688:97-126
pubmed: 20938835
Mol Cells. 2016 May 31;39(5):382-8
pubmed: 27025386
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Orphanet J Rare Dis. 2013 Mar 15;8:41
pubmed: 23497566
NPJ Genom Med. 2017;2:
pubmed: 29152331
BMC Med Genet. 2015 Sep 21;16:84
pubmed: 26392352
Eur J Neurol. 2018 Jun;25(6):841-847
pubmed: 29498452
Hum Mol Genet. 2018 Dec 15;27(24):4263-4272
pubmed: 30215711
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Clin Genet. 2018 Feb;93(2):301-309
pubmed: 28708278
Brain. 2016 Nov 1;139(11):2844-2854
pubmed: 27604308
Neuromuscul Disord. 2013 Dec;23(12):1081-111
pubmed: 24446552
Genet Med. 2018 Dec;20(12):1554-1563
pubmed: 29543227
Nat Commun. 2019 Mar 27;10(1):1396
pubmed: 30918256
Genet Med. 2019 Jan;21(1):173-180
pubmed: 29765138
Neuromuscul Disord. 2018 Dec;28(12):1031-1063
pubmed: 30472062
Clin Genet. 2011 Oct;80(4):334-45
pubmed: 21291453
Neuromuscul Disord. 2016 Nov;26(11):744-748
pubmed: 27751653
Brain. 2015 Apr;138(Pt 4):836-44
pubmed: 25681410
J Neurol. 2013 Aug;260(8):2084-93
pubmed: 23670307
Genome Biol. 2015 Oct 13;16:226
pubmed: 26463453
Neuromuscul Disord. 2017 Nov;27(11):997-1008
pubmed: 28967462
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
pubmed: 271968
Hum Mutat. 2018 Sep;39(9):1284-1298
pubmed: 29858556
Brain. 2016 Mar;139(Pt 3):674-91
pubmed: 26700687
Neurol Genet. 2015 Aug 13;1(2):e14
pubmed: 27066551
J Med Genet. 2004 Apr;41(4):e50
pubmed: 15060126
F1000Res. 2018 Dec 11;7:
pubmed: 30631434
Neurology. 2003 Jun 10;60(11):1805-10
pubmed: 12796535