Mutations in the tail domain of MYH3 contributes to atrial septal defect.
Adolescent
Adult
Amino Acid Sequence
Amino Acid Substitution
Base Sequence
Case-Control Studies
Child
Child, Preschool
Conserved Sequence
Cytoskeletal Proteins
/ chemistry
Female
Heart Septal Defects, Atrial
/ genetics
Humans
Male
Middle Aged
Models, Genetic
Models, Molecular
Mutation
Mutation, Missense
Myosin Heavy Chains
/ chemistry
Myosin Type III
/ chemistry
Polymorphism, Single Nucleotide
Young Adult
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
11
2019
accepted:
12
03
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
11
7
2020
Statut:
epublish
Résumé
Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
Identifiants
pubmed: 32315303
doi: 10.1371/journal.pone.0230982
pii: PONE-D-19-32624
pmc: PMC7173802
doi:
Substances chimiques
Cytoskeletal Proteins
0
MYH3 polypeptide, human
0
Myosin Type III
EC 3.6.1.-
Myosin Heavy Chains
EC 3.6.4.1
Banques de données
Dryad
['10.5061/dryad.pvmcvdnh3']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0230982Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Med J Malaysia. 2000 Dec;55(4):424-32
pubmed: 11221153
Clin Res Cardiol. 2011 Dec;100(12):1111-7
pubmed: 21909849
J Pediatr. 2010 May;156(5):782-5
pubmed: 20138303
Science. 2002 Jun 21;296(5576):2225-9
pubmed: 12029063
Clin Genet. 2010 Aug;78(2):103-23
pubmed: 20497191
Nucleic Acids Res. 2009 May;37(9):e67
pubmed: 19339519
Circ Res. 2017 Mar 17;120(6):923-940
pubmed: 28302740
BMC Pregnancy Childbirth. 2016 Mar 22;16:61
pubmed: 27006092
Ann Neurol. 1998 Aug;44(2):242-8
pubmed: 9708547
Hum Mutat. 2000;15(1):7-12
pubmed: 10612815
Int J Epidemiol. 2019 Apr 1;48(2):455-463
pubmed: 30783674
Am J Hum Genet. 2015 May 7;96(5):841-9
pubmed: 25957469
Nat Genet. 2005 Apr;37(4):423-8
pubmed: 15735645
Med Sci Monit. 2019 Apr 15;25:2756-2763
pubmed: 30982828
J Pediatr. 2008 Dec;153(6):807-13
pubmed: 18657826
Arch Dis Child. 2017 Jun;102(6):496-502
pubmed: 27986699
Eur J Med Res. 2018 Apr 27;23(1):20
pubmed: 29703267
Cell Mol Life Sci. 2013 Apr;70(7):1221-39
pubmed: 22955375
Nat Genet. 2006 May;38(5):561-5
pubmed: 16642020
PLoS One. 2014 Sep 10;9(8):e106806
pubmed: 25207942
Neurology. 2002 Mar 12;58(5):780-6
pubmed: 11889243
Acta Neuropathol. 2013 Jan;125(1):3-18
pubmed: 22918376
J Med Assoc Thai. 2015 Jan;98(1):7-13
pubmed: 25775725
Hum Mol Genet. 2010 Oct 15;19(20):4007-16
pubmed: 20656787
Genet Epidemiol. 2009 Nov;33(7):581-98
pubmed: 19278015
J Am Coll Cardiol. 2011 Nov 15;58(21):2241-7
pubmed: 22078432
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Am J Hum Genet. 2004 Oct;75(4):703-8
pubmed: 15322983
Arch Neurol. 2008 Aug;65(8):1083-90
pubmed: 18695058
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12559-64
pubmed: 11058170
Eur Heart J. 2018 Mar 21;39(12):999-1001
pubmed: 29194471
Lancet. 2014 May 31;383(9932):1921-32
pubmed: 24725467
RNA. 2008 May;14(5):802-13
pubmed: 18369186
Development. 2011 Sep;138(18):3955-66
pubmed: 21862559
Ann Neurol. 2003 Oct;54(4):494-500
pubmed: 14520662
Neurology. 2005 Feb 8;64(3):527-9
pubmed: 15699387
J Bone Joint Surg Am. 2011 Jun 1;93(11):1045-50
pubmed: 21531865