In the original article, we noted two mutation annotation errors. The correction of these two mistakes does not change the scientific conclusions in any way. The authors apologize for these nomenclature errors. Please find below the corrected annotations of those two mutations:
(1) The correct RNA and protein annotations of the SMAD6 variant in P99 are c.455_461del and p.Pro152Profs*27, and not c.454_461del and p.Gly166Valfs*23.
(2) The correct RNA and protein annotations of the SMAD6 variant in P128 are c.74_79del and p.Ser27_Gly28del, and not c.73_79del and p.Gly26_Ser27del.
As a consequence, a correction has been made to RESULTS, Paragraphs 5 and 6:
The SMAD6 c.726del variant leads to a frameshift (p.Lys242Asnfs*300) and a predicted protein with a C-terminal extension due to loss of the intended stop codon. The c.455_461del frameshift variant (p.Pro152Profs*27) causes the introduction of a premature stop codon, most likely resulting in haploinsufficiency due to nonsense-mediated mRNA decay (NMD). Also the two nonsense variants (p.Tyr279* and p.Tyr288*) are predicted to lead to NMD. All of the missense variants cluster in the functionally important MH1 and MH2 domains (Makkar et al., 2009) (amino acids 148–275 and 331–496, respectively), which is not the case for the sole missense variant (p.Ser130Leu) found in a control individual (Figure 2). All but one (p.Arg443His) of the identified variants were absent in the ExAC control cohort (v0.3.1; Supplementary Table 2). Moreover, the missense variants in the patient cohort (7/7) are enriched in the MH1 and MH2 domains when compared to ExAC controls (n = 228/430; p = 0.02).
Figure 2
For two SMAD6 mutation carriers (P89, p.Gly271Glu; P99, p.Pro152Profs*27), gDNA of family members was available for segregation analysis (Supplementary Figure 1). Although neither of these probands had a documented family history of BAV/TAA, a brother of P89 has been diagnosed with a sinus of Valsalva aneurysm (45 mm) and carried the SMAD6 mutation. The mutation was also observed in an unaffected daughter (age 28) of the proband (Supplementary Figure 1). Three unaffected siblings at ages 54, 58, and 64 did not carry the mutation. No gDNA was available from a sister of P99 with unspecified aortic valve problems. The p.Pro152Profs*27 mutation was found in an unaffected daughter (age 39) of P99 but was absent in his 37 year-old unaffected son (Supplementary Figure 1).
We also provide a corrected Figure 2 and Supplementary Table 2.
Statements
Conflict of interest
The 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.
Supplementary material
The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fphys.2017.00730/full#supplementary-material
References
1
MakkarP.MetpallyR. P.SangadalaS.ReddyB. V. (2009). Modeling and analysis of MH1 domain of Smads and their interaction with promoter DNA sequence motif. J. Mol. Graph. Model.27, 803–812. 10.1016/j.jmgm.2008.12.003
Summary
Keywords
bicuspid aortic valve, thoracic aortic aneurysm, SMAD6, targeted gene panel, variant burden test
Citation
Gillis E, Kumar AA, Luyckx I, Preuss C, Cannaerts E, van de Beek G, Wieschendorf B, Alaerts M, Bolar N, Vandeweyer G, Meester J, Wünnemann F, Gould RA, Zhurayev R, Zerbino D, Mohamed SA, Mital S, Mertens L, Björck HM, Franco-Cereceda A, McCallion AS, Van Laer L, Verhagen JMA, van de Laar IMBH, Wessels MW, Messas E, Goudot G, Nemcikova M, Krebsova A, Kempers M, Salemink S, Duijnhouwer T, Jeunemaitre X, Albuisson J, Eriksson P, Andelfinger G, Dietz HC, Verstraeten A, Loeys BL and Mibava Leducq Consortium (2017) Corrigendum: Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor. Front. Physiol. 8:730. doi: 10.3389/fphys.2017.00730
Received
09 August 2017
Accepted
08 September 2017
Published
25 September 2017
Volume
8 - 2017
Edited and reviewed by
Gerald A. Meininger, University of Missouri, United States
Updates
Copyright
© 2017 Gillis, Kumar, Luyckx, Preuss, Cannaerts, van de Beek, Wieschendorf, Alaerts, Bolar, Vandeweyer, Meester, Wünnemann, Gould, Zhurayev, Zerbino, Mohamed, Mital, Mertens, Björck, Franco-Cereceda, McCallion, Van Laer, Verhagen, van de Laar, Wessels, Messas, Goudot, Nemcikova, Krebsova, Kempers, Salemink, Duijnhouwer, Jeunemaitre, Albuisson, Eriksson, Andelfinger, Dietz, Verstraeten, Loeys and Mibava Leducq Consortium.
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*Correspondence: Bart L. Loeys bart.loeys@uantwerpen.be
This article was submitted to Vascular Physiology, a section of the journal Frontiers in Physiology
†These authors have contributed equally to this work.
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