Reply to: “SLC40A1-R178G or R178Q and ferroportin disease? A call for vigilance in mutation reporting”
Authors: Matthaios Speletas, Anna Kioumi, Anastasios E. Germenis
Journal: Journal of Hepatology (2013)

SLC40A1-R178G or R178Q and ferroportin disease? A call for vigilance in mutation reportingJournal of HepatologyVol. 59Issue 2PreviewI refer to a previous Letter to the Editor and its reply [1] regarding the excellent meta-analysis on ferroportin disease performed by Mayr et al. in the Journal of Hepatology in November 2010 [2]. The SLC40A1-R178G mutation is discussed and whether it is a disease-causing mutation with incomplete penetrance or a polymorphism. Upon further inspection of the original report by Speletas et al., describing the R178G mutation in a Greek family, published in the journal Blood Cell Molecules and Diseases in 2008 [3], I have come to the conclusion that an error was made in the designation of this mutation. Full-Text PDF Open Access We appreciate the observation by Dr. Wallace uncovering our error in citing unwittingly the nomenclature of amino acid alteration of the mutation g.963G>A (according to the NCBI reference sequence NM_014585) of SLC40A1 gene, as R178G (Arg178Gly) instead of R178Q (Arg178Gln). An Erratum has already been submitted in concern to our initial publication [[1]Speletas M. Kioumi A. Loules G. Hytiroglou P. Tsitouridis J. Christakis J. et al.Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV.Blood Cells Mol Dis. 2008; 40: 353-359Crossref PubMed Scopus (20) Google Scholar]. We have to emphasize that all the data presented in both our initial publication describing this alteration and in the Letter to the Editor [[2]Speletas M. Onoufriadis E. Kioumi A. Germenis A.E. SLC40A1-R178G mutation and ferroportin disease.J Hepatol. 2011; 55 (author reply 731–732): 730-731Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar] are absolutely correct. At the time of the submission of the initial publication in Blood Cells Molecules and Diseases, this alteration (R178Q) was really novel, as the paper of Cunat et al. [[3]Cunat S. Giansily-Blaizot M. Bismuth M. Blanc F. Dereure O. Larrey D. et al.Global sequencing approach for characterizing the molecular background of hereditary iron disorders.Clin Chem. 2007; 53: 2060-2069Crossref PubMed Scopus (29) Google Scholar] had not appeared in the literature. Unfortunately, a database of ferroportin gene (SLC40A1) mutations is not yet available. It would be worthy such a database to be established for SLC40A1, as it is the rule for other genes of clinical interest. Very usefully, a formal and detailed review of the incoming alterations is provided by such databases. To the end, we have recently performed a detailed bioinformatic analysis in order to assess whether this alteration is likely to be deleterious and, if possible, to determine which aspects of protein function are affected. For this purpose, we used two different software packages, namely SIFT (Sorting Intolerant From Tolerant; available at: http://sift.bii.a-star.edu.sg/) and PolyPhen2 (available at: http://genetics.bwh.harvard.edu.pph2/) and we determined that the R178Q mutation is rather deleterious for protein function (intolerant on SIFT analysis with a probability score 0.00, and probably damaging on PolyPhen2 analysis: sensitivity score 0.00, specificity score: 1.00), causing the emergence of the classical ferroportin disease. We honestly apologize for our mistake. Such mistakes would be really avoided using the cDNA numbering position rather than nucleotide positions obtained from NCBI reference sequences (that are regularly updated) and the presentation of amino acid substitutions by both three letter and single letter codes, as it is rightly proposed by Dr. Wallace. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.