Novel mutations in MYBPC1 are associated with myogenic tremor and mild myopathy.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
26
09
2018
revised:
23
04
2019
accepted:
25
04
2019
pubmed:
27
4
2019
medline:
31
3
2020
entrez:
27
4
2019
Statut:
ppublish
Résumé
To define a distinct, dominantly inherited, mild skeletal myopathy associated with prominent and consistent tremor in two unrelated, three-generation families. Clinical evaluations as well as exome and panel sequencing analyses were performed in affected and nonaffected members of two families to identify genetic variants segregating with the phenotype. Histological assessment of a muscle biopsy specimen was performed in 1 patient, and quantitative tremor analysis was carried out in 2 patients. Molecular modeling studies and biochemical assays were performed for both mutations. Two novel missense mutations in MYBPC1 (p.E248K in family 1 and p.Y247H in family 2) were identified and shown to segregate perfectly with the myopathy/tremor phenotype in the respective families. MYBPC1 encodes slow myosin binding protein-C (sMyBP-C), a modular sarcomeric protein playing structural and regulatory roles through its dynamic interaction with actin and myosin filaments. The Y247H and E248K mutations are located in the NH Here, we link two novel missense mutations in MYBPC1 with a dominant, mild skeletal myopathy invariably associated with a distinctive tremor. The molecular, genetic, and clinical studies are consistent with a unique sarcomeric origin of the tremor, which we classify as "myogenic tremor." ANN NEUROL 2019.
Identifiants
pubmed: 31025394
doi: 10.1002/ana.25494
pmc: PMC6685440
mid: NIHMS1041971
doi:
Substances chimiques
Carrier Proteins
0
myosin-binding protein C
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
129-142Subventions
Organisme : NIAMS NIH HHS
ID : R21 AR072981
Pays : United States
Organisme : Muscular Dystrophy Association
ID : 313579
Pays : International
Organisme : NIAMS NIH HHS
ID : T32 AR007592
Pays : United States
Organisme : NIH/NINDS
Pays : International
Organisme : European Regional Development Fund
ID : 2010/0223/2DP/2.1.1.1.0/10/APIA/VIAA/025
Pays : International
Organisme : NSF RUI
ID : MCB-1607024
Pays : International
Organisme : Latvian Council of Science State funding
Pays : International
Organisme : Muscular Dystrophy Association
ID : 602614
Pays : International
Informations de copyright
© 2019 American Neurological Association.
Références
Am J Hum Genet. 2000 Oct;67(4):814-21
pubmed: 10952871
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14614-9
pubmed: 11114175
Neuromuscul Disord. 2001 Jan;11(1):11-9
pubmed: 11166161
Hum Mutat. 2003 Jun;21(6):577-81
pubmed: 12754702
Circ Res. 2004 May 28;94(10):1279-89
pubmed: 15166115
Clin Neurophysiol. 2004 Sep;115(9):2151-6
pubmed: 15294218
Am J Hum Genet. 2004 Oct;75(4):703-8
pubmed: 15322983
J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):208-15
pubmed: 16103042
J Biol Chem. 2006 Mar 17;281(11):7666-83
pubmed: 16407297
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17713-7
pubmed: 17095604
Int J Biochem Cell Biol. 2007;39(12):2161-6
pubmed: 17320463
Mol Biol Cell. 2009 Jun;20(12):2963-78
pubmed: 19403693
Nat Protoc. 2009;4(7):1073-81
pubmed: 19561590
Hum Mol Genet. 2010 Apr 1;19(7):1165-73
pubmed: 20045868
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
J Biomed Biotechnol. 2010;2010:652065
pubmed: 20396395
Neurology. 2010 Aug 24;75(8):732-41
pubmed: 20733148
J Biol Chem. 2011 Jan 21;286(3):2008-16
pubmed: 21071444
Biochem J. 2011 Jun 1;436(2):437-45
pubmed: 21426302
J Proteome Res. 2011 Oct 7;10(10):4547-55
pubmed: 21888435
J Biol Chem. 2012 Mar 9;287(11):8254-62
pubmed: 22235120
Circ Res. 2012 Jun 8;110(12):1585-95
pubmed: 22581927
Neuromuscul Disord. 2012 Dec;22(12):1096-104
pubmed: 22784669
Nat Protoc. 2012 Jul 19;7(8):1511-22
pubmed: 22814390
Acta Neuropathol. 2013 Jan;125(1):3-18
pubmed: 22918376
Proc Natl Acad Sci U S A. 1990 Mar;87(6):2157-61
pubmed: 2315308
BMC Genet. 2012 Nov 15;13:99
pubmed: 23153285
Brain. 2013 Jan;136(Pt 1):282-93
pubmed: 23365102
FASEB J. 2013 Aug;27(8):3217-28
pubmed: 23657818
Front Physiol. 2013 Dec 25;4:391
pubmed: 24399972
Neuromuscul Disord. 2014 Feb;24(2):97-116
pubmed: 24456932
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Nat Methods. 2014 Apr;11(4):361-2
pubmed: 24681721
Bioinformatics. 2014 Oct 15;30(20):2981-2
pubmed: 24996895
Muscle Nerve. 2015 May;51(5):767-72
pubmed: 25430424
Neuromuscul Disord. 2015 Feb;25(2):155-60
pubmed: 25447691
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Brain. 2015 Feb;138(Pt 2):246-68
pubmed: 25552303
Clin Neurophysiol. 2015 Sep;126(9):1817-24
pubmed: 25641441
PLoS One. 2015 Feb 13;10(2):e0117158
pubmed: 25679999
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Nat Protoc. 2015 Jun;10(6):845-58
pubmed: 25950237
Sci Rep. 2015 Aug 19;5:12637
pubmed: 26285797
Sci Rep. 2015 Aug 19;5:13235
pubmed: 26287277
J Vet Intern Med. 2015 Sep-Oct;29(5):1418-21
pubmed: 26289121
Muscle Nerve. 2016 Apr;53(4):564-9
pubmed: 26296490
J Mol Biol. 2016 Feb 22;428(4):720-725
pubmed: 26410586
Ann Neurol. 2015 Dec;78(6):982-994
pubmed: 26418456
Nucleic Acids Res. 2016 Jan 4;44(D1):D862-8
pubmed: 26582918
Clin Genet. 2016 Jul;90(1):84-9
pubmed: 26661508
Mamm Genome. 2016 Oct;27(9-10):495-502
pubmed: 27215641
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Front Physiol. 2016 Sep 14;7:410
pubmed: 27683561
Sci Adv. 2017 Jun 09;3(6):e1603213
pubmed: 28630918
Acta Neurol Scand. 1995 Aug;92(2):122-6
pubmed: 7484058
J Cell Biol. 1993 Nov;123(3):619-26
pubmed: 8227129
Eur J Biochem. 1993 Sep 1;216(2):661-9
pubmed: 8375400
Eur J Biochem. 1996 Jan 15;235(1-2):317-23
pubmed: 8631348
Electroencephalogr Clin Neurophysiol. 1996 Oct;101(5):461-8
pubmed: 8913201
Ann Neurol. 1998 Aug;44(2):242-8
pubmed: 9708547