NGS in Hereditary Ataxia: When Rare Becomes Frequent.
Genesis
HA
TRP
cohort
diagnostic yield
exome sequencing
mutation
next-generation sequencing
targeted resequencing panel
variant
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
06 Aug 2021
06 Aug 2021
Historique:
received:
23
06
2021
revised:
03
08
2021
accepted:
04
08
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
25
9
2021
Statut:
epublish
Résumé
The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis.
Identifiants
pubmed: 34445196
pii: ijms22168490
doi: 10.3390/ijms22168490
pmc: PMC8395181
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero della Salute
ID : RF2016
Références
Eur J Neurol. 2021 Aug;28(8):2784-2788
pubmed: 33851480
Cerebellum. 2019 Feb;18(1):137-146
pubmed: 30078120
Brain Dev. 2016 May;38(5):498-506
pubmed: 26686600
Ann Clin Transl Neurol. 2020 Apr;7(4):595-601
pubmed: 32237276
Clin Genet. 2017 Jan;91(1):86-91
pubmed: 27062503
Ann Clin Transl Neurol. 2020 Jan;7(1):105-111
pubmed: 31854126
Parkinsonism Relat Disord. 2019 Aug;65:91-96
pubmed: 31126790
Brain Sci. 2021 Feb 16;11(2):
pubmed: 33669240
Ann Neurol. 2005 May;57(5):777
pubmed: 15852392
Nucleic Acids Res. 2018 Jul 2;46(W1):W350-W355
pubmed: 29718330
Mitochondrion. 2010 Aug;10(5):510-5
pubmed: 20580948
PLoS One. 2017 Mar 31;12(3):e0174667
pubmed: 28362824
Brain. 2017 Jun 1;140(6):1579-1594
pubmed: 28444220
Genet Med. 2020 Dec;22(12):2114-2119
pubmed: 32741968
J Child Neurol. 2013 Oct;28(10):1292-5
pubmed: 22914369
Hum Mutat. 2018 Dec;39(12):2060-2071
pubmed: 30252181
Neurol Sci. 2020 Sep;41(9):2423-2432
pubmed: 32342324
J Neurol. 2021 May;268(5):1927-1937
pubmed: 33417001
Eur J Neurol. 2020 Mar;27(3):498-505
pubmed: 31571321
Eur J Hum Genet. 2003 Jul;11(7):547-9
pubmed: 12825077
Nat Genet. 2006 Jan;38(1):93-100
pubmed: 16311595
Orphanet J Rare Dis. 2013 Oct 28;8:173
pubmed: 24164873
Hum Mutat. 2014 Jan;35(1):45-9
pubmed: 24108619
J Neurol. 2021 Sep;268(9):3381-3389
pubmed: 33704555
Mov Disord Clin Pract. 2019 Oct 23;6(8):724-726
pubmed: 31745488
Neurology. 2014 May 13;82(19):1749-50
pubmed: 24719489
Hum Mutat. 2020 Feb;41(2):487-501
pubmed: 31692161
Ann Neurol. 2016 Oct;80(4):
pubmed: 27543892
Brain. 2014 Jan;137(Pt 1):69-77
pubmed: 24355708
Brain Dev. 2020 Jan;42(1):6-18
pubmed: 31493945
Nucleic Acids Res. 2017 Jul 3;45(W1):W229-W235
pubmed: 28525590
Mol Genet Genomic Med. 2018 Nov;6(6):1041-1052
pubmed: 30293248
Neurol Genet. 2020 Jun 5;6(4):e444
pubmed: 32637629
Cerebellum. 2018 Jun;17(3):380-385
pubmed: 29248984
J Neurol. 2021 Jul 22;:
pubmed: 34292398
Pacing Clin Electrophysiol. 2018 Sep;41(9):1078-1092
pubmed: 29953624
Eur J Hum Genet. 2016 Aug;24(9):1262-7
pubmed: 26932191
Nat Rev Dis Primers. 2019 Apr 11;5(1):24
pubmed: 30975995
JAMA Neurol. 2014 Oct;71(10):1305-10
pubmed: 25089919
Ann Neurol. 2002 Aug;52(2):211-9
pubmed: 12210792
J Peripher Nerv Syst. 2020 Jun;25(2):117-124
pubmed: 32096284
Am J Hum Genet. 1996 Aug;59(2):320-30
pubmed: 8755918
JAMA Neurol. 2018 May 1;75(5):591-599
pubmed: 29482223
Mol Cell Endocrinol. 2001 Jan 22;171(1-2):61-70
pubmed: 11165012
Am J Hum Genet. 2015 Feb 5;96(2):309-17
pubmed: 25658047
J Child Neurol. 2016 Dec;31(14):1534-1539
pubmed: 27572814
Brain. 2017 Jun 1;140(6):1561-1578
pubmed: 28459997
Parkinsonism Relat Disord. 2020 Jul;76:42-43
pubmed: 32559632
JAMA Neurol. 2018 Oct 1;75(10):1234-1245
pubmed: 29913018
Eur J Neurol. 2019 Jan;26(1):80-86
pubmed: 30098094
CNS Neurosci Ther. 2019 Jan;25(1):21-29
pubmed: 29756269
Cerebellum. 2021 Feb;20(1):54-61
pubmed: 32816195
Neurol Sci. 2020 Oct;41(10):2989-2991
pubmed: 32367327
Neurogenetics. 2018 Jan;19(1):1-8
pubmed: 29209898
Eur J Endocrinol. 1997 Jul;137(1):40-7
pubmed: 9242200
JAMA Neurol. 2014 Oct;71(10):1237-46
pubmed: 25133958
Nat Genet. 2012 Apr 29;44(6):704-8
pubmed: 22544365
Cerebellum. 2019 Aug;18(4):817-822
pubmed: 31111429
J Neurol. 2015 Aug;262(8):1822-7
pubmed: 25976027
Hum Mutat. 2016 Dec;37(12):1340-1353
pubmed: 27528516
Hum Mutat. 2015 Oct;36(10):950-6
pubmed: 26173844
Ann Neurol. 2012 Dec;72(6):859-69
pubmed: 23280837
Science. 1996 Mar 8;271(5254):1423-7
pubmed: 8596916
Parkinsonism Relat Disord. 2019 May;62:215-220
pubmed: 30522958
J Med Genet. 1996 Dec;33(12):1022-6
pubmed: 9004136
Eur J Neurol. 2009 Feb;16(2):240-5
pubmed: 19138334
Mov Disord. 2013 Sep;28(10):1439-42
pubmed: 23801573
Brain. 2015 Feb;138(Pt 2):276-83
pubmed: 25497598
Clin Genet. 2015 Feb;87(2):e1-3
pubmed: 25477152
Am J Hum Genet. 1999 Jun;64(6):1617-31
pubmed: 10330348
Mov Disord Clin Pract. 2020 Jul 07;7(6):684-687
pubmed: 32775515
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Hum Mutat. 2020 Jul;41(7):1232-1237
pubmed: 32333447
Neurogenetics. 2013 Nov;14(3-4):225-32
pubmed: 24091540
Neurology. 2019 Jun 4;92(23):e2679-e2690
pubmed: 31068484
Nat Genet. 2000 Oct;26(2):207-10
pubmed: 11017079
Am J Hum Genet. 1999 Jun;64(6):1511-23
pubmed: 10330339
Brain. 2017 Nov 1;140(11):2860-2878
pubmed: 29053796
Neurology. 2018 Nov 20;91(21):e1988-e1998
pubmed: 30381368
J Neurol. 2016 Jul;263(7):1314-22
pubmed: 27142713
PLoS Comput Biol. 2014 Apr 24;10(4):e1003569
pubmed: 24762569
Hum Mol Genet. 2012 May 15;21(10):2205-10
pubmed: 22328086
Hum Mutat. 2010 Feb;31(2):191-6
pubmed: 19953606
Mov Disord. 2017 Mar;32(3):332-345
pubmed: 28195350
Brain. 2013 Oct;136(Pt 10):3106-18
pubmed: 24030952
Hum Genet. 1992 Mar;88(5):557-61
pubmed: 1348045
Pediatr Res. 2020 Feb;87(3):456-462
pubmed: 31266054
Parkinsonism Relat Disord. 2020 Nov;80:58-64
pubmed: 32961395
Mov Disord. 2006 Jul;21(7):1025-8
pubmed: 16547918
J Clin Neurosci. 2019 Sep;67:14-18
pubmed: 31272831
Neurology. 2008 Nov 4;71(19):1500-5
pubmed: 18799786
Genet Med. 2013 Sep;15(9):673-83
pubmed: 23538602
J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):301-309
pubmed: 27965395
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):925-30
pubmed: 11805335
Mov Disord Clin Pract. 2020 Sep 29;7(8):940-949
pubmed: 33163565
Neuron. 2019 Feb 20;101(4):560-583
pubmed: 30790538
J Clin Endocrinol Metab. 2014 Oct;99(10):E2067-75
pubmed: 25033069
Nat Genet. 2010 Apr;42(4):313-21
pubmed: 20208537
J Mol Diagn. 2006 Feb;8(1):128-32
pubmed: 16436644
Neurology. 2004 Oct 12;63(7):1251-7
pubmed: 15477547
Brain. 2014 Oct;137(Pt 10):2657-63
pubmed: 25070513
Am J Med Genet A. 2017 Jan;173(1):207-212
pubmed: 27862915
Neuroradiology. 2020 Sep;62(9):1095-1103
pubmed: 32285148
Clin Genet. 2019 Dec;96(6):566-574
pubmed: 31429931
Am J Hum Genet. 2015 Nov 5;97(5):726-37
pubmed: 26456284
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W314-9
pubmed: 24829462
Neurogenetics. 2020 Jan;21(1):59-66
pubmed: 31741144
Genet Med. 2019 Jan;21(1):195-206
pubmed: 29915382
J Med Genet. 2015 Feb;52(2):85-94
pubmed: 25480986
Trends Genet. 2018 Sep;34(9):666-681
pubmed: 29941292
Nat Genet. 1997 May;16(1):88-92
pubmed: 9140401
Neuroepidemiology. 2014;42(3):174-83
pubmed: 24603320
Neurology. 2016 Mar 8;86(10):954-62
pubmed: 26865513
Handb Clin Neurol. 2018;155:73-89
pubmed: 29891078
Genome Biol. 2011 Sep 14;12(9):227
pubmed: 21920052
Genet Med. 2020 Nov;22(11):1851-1862
pubmed: 32713943
Eur J Hum Genet. 2016 Oct;24(10):1460-6
pubmed: 27165006
Am J Hum Genet. 2008 Mar;82(3):780-5
pubmed: 18313024
PLoS One. 2016 Apr 14;11(4):e0153283
pubmed: 27077743
Bioinformatics. 2014 Feb 01;30(3):335-42
pubmed: 24281696