A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient
Open accessAbstract
Background: A severe form of iron overload with the clinicopathological features of haemochromatosis inherited in an autosomal dominant manner has been described in the Solomon Islands. The genetic basis of the disorder has not been identified. The disorder has similarities to type 4 haemochromatosis, which is caused by mutations in ferroportin1. Aims: The aims of this study were to identify the genetic basis of iron overload in a patient from the Solomon Islands. Patient and methods: Genomic DNA was isolated from peripheral blood leucocytes of a Solomon Islands man with severe iron overload. The entire coding region and splice sites of the ferroportin1 gene was sequenced. Results and conclusions: A novel missense mutation (431A>C; N144T) was identified in exon 5 of the ferroportin1 gene. A novel restriction endonuclease based assay which identifies both the N144T and N144H mutations was developed which will simplify the diagnosis and screening of patients for iron overload in the Solomon Islands and other populations. This is the first identified mutation associated with haemochromatosis in the Solomon Islands population.
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Several FPN mutations decrease hepcidin binding to FPN, including N144H/D/T, C326S/F/Y, Y333H, Y501C, D504N and H507R.
“Several FPN mutations decrease hepcidin binding to FPN, including N144H/D/T 34-36 , C326S/F/Y 13,29-31 , Y333H 37 , Y501C 7,38 , D504N 7,39 and H507R 32 .”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [36]
The Results and Discussion identify N144T in a Solomon Islands patient and discuss the previously reported N144H mutation. The paper does not report decreased hepcidin binding for either mutation, nor does it address N144D or the other listed mutations. Its mention of hepcidin concerns mutations in the hepcidin gene, not binding to ferroportin. (LLM, conf=0.84)
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Cites
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664 · see citing works
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667 · see citing works
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422 · see citing works
A Novel Mammalian Iron-regulated Protein Involved in Intracellular Iron Metabolism
Abboud, S., & Haile, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000713200 · Cited by 1,267 · see citing works
Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis
Roetto, A., Papanikolaou, G., Politou, M., Alberti, F., Girelli, D., Christakis, J., Loukopoulos, D., & Camaschella, C. (2003) · Nature Genetics · doi:10.1038/ng1053 · Cited by 860 · see citing works
The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22
Camaschella, C., Roetto, A., Calì, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., & Gasparini, P. (2000) · Nature Genetics · doi:10.1038/75534 · Cited by 803 · see citing works
Autosomal-dominant hemochrom-atosis is associated with a mutation in the ferroportin (SLC11A3) gene
Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., & Pietrangelo, A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113468 · Cited by 557 · see citing works
Autosomal-dominant hemochrom-atosis is associated with a mutation in the ferroportin (SLC11A3) gene
Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., & Pietrangelo, A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13468 · Cited by 555 · see citing works
A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis
Njajou, O. T., Vaessen, N., Joosse, M., Berghuis, B., van Dongen, J. W. F., Breuning, M. H., Snijders, P. J. L. M., Rutten, W. P. F., Sandkuijl, L. A., Oostra, B. A., et al. (2001) · Nature Genetics · doi:10.1038/90038 · Cited by 492 · see citing works
Juvenile Hemochromatosis Locus Maps to Chromosome 1q
Roetto, A., Totaro, A., Cazzola, M., Cicilano, M., Bosio, S., D’Ascola, D. G., Carella, M., Zelante, L., Kelly, A., Cox, T. M., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302379 · Cited by 235 · see citing works
Devalia, V., Carter, K., Walker, A. P., Perkins, S. J., Worwood, M., May, A. M., & Dooley, J. S. (2002) · Blood · doi:10.1182/blood-2001-11-0132 · Cited by 188 · see citing works
A novel MHC class-I-like gene is mutated in patients with hereditary haemochromatosis
(1996) · Trends in Genetics · doi:10.1016/0168-9525(96)81483-1 · Cited by 183 · see citing works
Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis
Wallace, D. F., Pedersen, P. L., Dixon, J. L., Stephenson, P. M., Searle, J. W., Powell, L. W., & Subramaniam, V. N. (2002) · Blood · doi:10.1182/blood.v100.2.692 · Cited by 173 · see citing works
Self-citationA valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4?
Roetto, A., Merryweather‐Clarke, A. T., Daraio, F., Livesey, K., Pointon, J. J., Barbabietola, G., Piga, A. G., Mackie, P. H., Robson, K., & Camaschella, C. (2002) · Blood · doi:10.1182/blood-2002-03-0693 · Cited by 102 · see citing works
Cazzola, M., Cremonesi, L., Papaioannou, M., Soriani, N., Kioumi, A., Charalambidou, A., Paroni, R. C., Romtsou, K., Levi, S., Ferrari, M., et al. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03946.x · Cited by 92 · see citing works
Familial iron overload with possible autosomal dominant inheritance
Eason, R. J., Adams, P. C., Aston, C. E., & Searle, J. W. (1990) · Australian and New Zealand Journal of Medicine · doi:10.1111/j.1445-5994.1990.tb01024.x · Cited by 60 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hereditary Hemochromatosis — A New Look at an Old Disease
Pietrangelo, A. (2004) · New England Journal of Medicine · doi:10.1056/nejmra031573 · Cited by 992 · see citing works
Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms
Billesbølle, C. B., Azumaya, C. M., Kretsch, R. C., Powers, A. S., Gonen, S., Schneider, S., Arvedson, T., Dror, R. O., Cheng, Y., & Manglik, A. (2020) · Nature · doi:10.1038/s41586-020-2668-z · Cited by 344 · see citing works
Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin
Drakesmith, H., Schimanski, L. M., Ormerod, E., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., et al. (2005) · Blood · doi:10.1182/blood-2005-02-0561 · Cited by 264 · see citing works
The molecular basis of ferroportin-linked hemochromatosis
De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., & Kaplan, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503804102 · Cited by 230 · see citing works
In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations
Schimanski, L. M., Drakesmith, H., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., Robson, K. J. H., et al. (2005) · Blood · doi:10.1182/blood-2004-11-4502 · Cited by 212 · see citing works
Ferroportin disease: pathogenesis, diagnosis and treatment
Pietrangelo, A. (2017) · Haematologica · doi:10.3324/haematol.2017.170720 · Cited by 151 · see citing works
Sham, R. L., Phatak, P. D., West, C., Lee, P., Andrews, C., & Beutler, E. (2005) · Blood Cells, Molecules, and Diseases · doi:10.1016/j.bcmd.2004.12.002 · Cited by 146 · see citing works
Ferroportin disease: a systematic meta-analysis of clinical and molecular findings
Mayr, R., Janecke, A. R., Schranz, M., Griffiths, W. J. H., Vogel, W., Pietrangelo, A., & Zoller, H. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.05.016 · Cited by 133 · see citing works
Wallace, D. F., Clark, R. M., Harley, H. A. J., & Subramaniam, V. N. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2003.12.008 · Cited by 83 · see citing works
Self-citationGenetic mechanisms and modifying factors in hereditary hemochromatosis
Weiss, G. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.201 · Cited by 82 · see citing works
Mok, H., Jelinek, J., Pai, S., Cattanach, B. M., Prchal, J. T., Youssoufian, H., & Schumacher, A. (2004) · Development · doi:10.1242/dev.01081 · Cited by 73 · see citing works
Vlasveld, L. T., Janssen, R., Bardou-Jacquet, E., Venselaar, H., Hamdi-Roze, H., Drakesmith, H., & Swinkels, D. W. (2019) · Pharmaceuticals · doi:10.3390/ph12030132 · Cited by 57 · see citing works
- Authors
- Arden, K. E., Wallace, D. F., Dixon, J. L., Summerville, L., Searle, J. W., Anderson, G. J., Ramm, G. A., Powell, L. W., & Subramaniam, V. N.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- The University of Queensland (AU)
- Corresponding author
- Subramaniam, V N
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2003-07-15
- Volume
- 52
- Issue
- 8
- Pages
- 1215-1217
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1773758
- OpenAlex
- W2148831846
- Cited by
- 84
- References
- 17
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (1r01dk057648-01)
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK057648, 5R01DK057648-02)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- SLC40A1, hemochromatosis, iron overload, novel missense mutation, genetic diagnosis, iron overload screening
- MeSH terms
- Hemochromatosis Protein, Ferroportin, Hemochromatosis, Humans, Male, Melanesia, Membrane Proteins, Middle Aged, Histocompatibility Antigens Class I, Sequence Analysis, DNA, Mutation, Missense, Cation Transport Proteins
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