CORRESPONDENCE: LETTERS TO THE EDITOR
Reply
Sara L. Van Driest, BA,
Vlad C. Vasile, MD,
Steve R. Ommen, MD, FACC,
Melissa L. Will, BS,
A. Jamil Tajik, MD, FACC,
Bernard J. Gersh, MD, FACC and
Michael J. Ackerman, MD, PhD*
* Sudden Death Genomics Laboratory, 501 Guggenheim, 200 First Street SW, Rochester, MN 55905 (Email: ackerman.michael{at}mayo.edu).
In their letter to the editor, Hermida and colleagues illuminate an issue of ever-increasing importance not only to pathogenetic studies involving hypertrophic cardiomyopathy (HCM), but for genomics research as a whole. Their letter calls for standardization of the format for mutation nomenclature to previously published recommendations (1,2). Indeed, our laboratory has conformed to alternate published recommendations (3), and a perusal of the HCM mutation literature quickly reveals that each laboratory has developed its own style for mutation reporting.
The pitfalls associated with mutation-formatting inconsistencies are illustrated in our own study (4), where owing to inconsistencies in published mutation nomenclature, three previously reported mutations in MYBPC3 were mistakenly reported as novel. The K811del in exon 25 was previously annotated as "exon 25 deletion 3 bp codon 811–815" (5). Exon 13, del c, D389 fs/15 was previously reported as "exon 14 del of c at nt 1200" (6). Finally, exon 29, ins aa, G1041 fs/5 was previously reported as "Ins AA1042" (7), and "exon 30, ins of AA at nt 3156" (6). Certainly, standardization of format as well as nucleotide and exon numbering in future publication will enhance data accuracy. However, several obstacles exist to the implementation of such standardization. Nomenclature schemes must be acceptable and, ideally, required uniformly by all publications. More importantly, any recognized scheme must be useful for colleagues with diverse research objectives including linkage analysis, candidate gene screening, functional characterization, and genetic counseling.
Furthermore, to enable the amalgamation of past mutation data with current and future discoveries including alternatively spliced transcripts, large-scale sequence variants, and changing "wild-type" genetic sequences, a dynamic compendium of sequence data is required. Indeed, this has been attempted at the genome level with the National Center for Biotechnology Information database (8), and tailored specifically for HCM by the Familial HCM DNA Mutation Database (9). Continued submission to, and support of, these resources will enable correlation of the vast data forthcoming with the foundational groundwork provided by published works. The request for standardization is much appreciated and has our complete endorsement.
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Footnotes
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Please note: Dr. Ackerman is supported by the Mayo Foundation, a Clinical Scientist Development Award from the Doris Duke Charitable Foundation, an Established Investigator Award from the American Heart Association, and the National Institutes of Health (HD42569).
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References
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- den Dunnen JT, Paalman MH. Standardizing mutation nomenclaturewhy bother?. Hum Mutat 2003;22:181-182.[CrossRef][Medline]
- den Dunnen JT, Antonarakis SE. Nomenclature for the description of human sequence variations Hum Genet 2001;109:121-124.[CrossRef][ISI][Medline]
- Antonarakis SE, Nomenclature Working Group Recommendations for a nomenclature system for human gene mutations Hum Mutat 1998;11:1-3.[CrossRef][ISI][Medline]
- Van Driest SL, Vasile VC, Ommen SR, et al. Myosin binding protein C mutations and compound herterozygosity in hypertrophic cardiomyopathy J Am Coll Cardiol 2004;44:1903-1910.[Abstract/Free Full Text]
- Jaaskelainen P, Kuusisto J, Miettinen R, et al. Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland J Mol Med 2002;80:412-422.[CrossRef][ISI][Medline]
- Erdmann J, Raible J, Maki-Abadi J, et al. Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy J Am Coll Cardiol 2001;38:322-330.[Abstract/Free Full Text]
- Niimura H, Bachinski LL, Sangwatanaroj S, et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy N Engl J Med 1998;338:1248-1257.[Abstract/Free Full Text]
- National Center for Biotechnology Information. Available at: http://www.ncbi.nlm.nih.gov/. Accessed April 1, 2005..
- DNA Mutation Database. Familial Hypertrophic Cardiomyopathy. Available at: http://www.angis.org.au/Databases/Heart/heartbreak.html. Accessed April 1, 2005..
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