Evidence of Two Novel
LGMDR23
hereditary myopathy
merosin
muscular dystrophy
next generation sequencing
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2022
2022
Historique:
received:
10
03
2022
accepted:
13
06
2022
entrez:
5
8
2022
pubmed:
6
8
2022
medline:
6
8
2022
Statut:
epublish
Résumé
Benefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team. In a multi-step approach, a thorough phenotype assessment including clinical examination, laboratory work, muscle MRI and histopathological evaluation of muscle was performed in combination with advanced Next Generation Sequencing (NGS). Different in-silico tools and prediction programs like Alamut, SIFT, Polyphen, MutationTaster and M-Cap as well as 3D- modeling of protein structure and RNA-sequencing were employed to determine clinical significance of the Two previously unknown sequence alterations in Two novel variants in
Sections du résumé
Background
UNASSIGNED
Benefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team.
Methods
UNASSIGNED
In a multi-step approach, a thorough phenotype assessment including clinical examination, laboratory work, muscle MRI and histopathological evaluation of muscle was performed in combination with advanced Next Generation Sequencing (NGS). Different in-silico tools and prediction programs like Alamut, SIFT, Polyphen, MutationTaster and M-Cap as well as 3D- modeling of protein structure and RNA-sequencing were employed to determine clinical significance of the
Results
UNASSIGNED
Two previously unknown sequence alterations in
Discussion
UNASSIGNED
Two novel variants in
Identifiants
pubmed: 35928135
doi: 10.3389/fneur.2022.893605
pmc: PMC9344914
doi:
Types de publication
Journal Article
Langues
eng
Pagination
893605Informations de copyright
Copyright © 2022 Meyer, Kaulfuß, Zechel, Kummer, Seif Amir Hosseini, Ernst, Schmidt, Pauli and Zschüntzsch.
Déclaration de conflit d'intérêts
Unrelated to this study SM has received payments for travel expenses from Alnylam, Kedrion, Momenta Pharmaceuticals, and Biogen. JS has received payments for advisory boards, speakers honoraria, travel expenses, research projects from Alnylam, Argenx, Biogen, BioMarin, Biotest, CSL Behring, Kezar, LFB, Novartis, Octapharma, Pfizer, and UCB. JZ has received payments for advisory boards, speakers honoraria, travel expenses, research projects from Alnylam, Biogen, Biotest, CSL Behring, Octapharma, Kedrion, Grifols, UCB, Hormosan, Alexion, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Ann N Y Acad Sci. 1990;580:195-213
pubmed: 2186690
Hum Mutat. 2018 Oct;39(10):1314-1337
pubmed: 30055037
J Biol Chem. 2009 Aug 21;284(34):22786-92
pubmed: 19553699
Curr Top Membr. 2015;76:31-60
pubmed: 26610911
J Cell Biol. 1994 Feb;124(3):381-94
pubmed: 8294519
J Neurol. 2022 May;269(5):2414-2429
pubmed: 34559299
Neuromuscul Disord. 1995 May;5(3):253-8
pubmed: 10712013
Muscle Nerve. 2015 Oct;52(4):547-53
pubmed: 25663498
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Muscle Nerve. 2011 Nov;44(5):703-9
pubmed: 21953594
Matrix Biol. 2018 Apr;67:32-46
pubmed: 29408412
Nat Genet. 1994 Nov;8(3):297-302
pubmed: 7874173
Proc Natl Acad Sci U S A. 1990 May;87(9):3264-8
pubmed: 2185464
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Structure. 2011 Jun 8;19(6):844-58
pubmed: 21645855
Cell Regul. 1990 Sep;1(10):731-40
pubmed: 2099832
C R Acad Sci III. 1994 Apr;317(4):351-7
pubmed: 8000914
Matrix Biol. 2018 Oct;71-72:188-204
pubmed: 29933045
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Neuromuscul Disord. 2010 Apr;20(4):241-50
pubmed: 20207543
J Cell Sci. 2008 May 15;121(Pt 10):1593-604
pubmed: 18430779
Appl Clin Genet. 2019 Jul 03;12:113-130
pubmed: 31308722
Curr Top Membr. 2015;76:1-30
pubmed: 26610910
Matrix Biol. 2004 Jan;22(7):521-38
pubmed: 14996432
Orphanet J Rare Dis. 2021 Jul 19;16(1):319
pubmed: 34281576
Front Genet. 2021 Aug 12;12:707087
pubmed: 34456976
Microsc Res Tech. 2008 May;71(5):349-56
pubmed: 18219670
Bioessays. 1996 Feb;18(2):123-32
pubmed: 8851045