Wilson’s Disease—Genetic Puzzles with Diagnostic Implications
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Genetic Diagnosis of WND
3.2. Genetic Counselling
3.3. Determination of the ATP7B Variants Pathogenicity
3.4. ATP7B Genotype—WND Phenotype Correlations
3.5. Rare Genetic Findings
3.6. Phenotype in Heterozygous WND Carriers
3.7. Genetic Co-Factors
3.8. Epigenetic Modifiers
4. Conclusions
Funding
Conflicts of Interest
Abbreviations
WND | Wilson’s disease |
KF ring | Kayser–Fleischer ring |
CP | ceruloplasmin |
NGS | next-generation sequencing |
RFLP | restriction fragments length polymorphism |
HRM | high-resolution melting |
NCBI | National Center of Biotechnological Information |
HSF | Human Splicing Finder |
References
- Walshe, J.M. History of Wilson’s disease: 1912 to 2000. Mov. Disord. 2006, 21, 142–147. [Google Scholar] [CrossRef]
- Steinberg, H.; Sternlieb, I. Wilson’s disease. In Major Problems in Internal Medicine; Saunders, W.B., Ed.; Wiley: Hoboken, NJ, USA, 1984; Volume XXIII. [Google Scholar] [CrossRef]
- Bearn, A.G. A genetical analysis of thirty families with Wilson’s disease (hepatolenticular degeneration). Ann. Hum. Genet. 1960, 24, 33–43. [Google Scholar] [CrossRef] [PubMed]
- Cumings, J.N. The effects of B.A.L. in hepatolenticular degeneration. Brain 1951, 74, 10–22. [Google Scholar] [CrossRef] [PubMed]
- Scheinberg, I.H.; Gitlin, D. Deficiency of CP in patients with hepatolenticular degeneration (Wilson’s disease). Science 1952, 116, 484–485. [Google Scholar] [CrossRef] [PubMed]
- Bull, P.C.; Thomas, G.R.; Rommens, J.M.; Forbes, J.R.; Cox, D.W. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat. Genet. 1993, 5, 327–337. [Google Scholar] [CrossRef] [PubMed]
- Tanzi, R.E.; Petrukhin, K.; Chernov, I.; Pellequer, J.L. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat. Genet. 1993, 5, 344–350. [Google Scholar] [CrossRef] [PubMed]
- Moini, M.; To, U.; Schilsky, M.L. Recent advances in Wilson disease. Transl. Gastroenterol. Hepatol. 2021, 6, 21. [Google Scholar] [CrossRef]
- Hasan, N.M.; Gupta, A.; Polishchuk, E.; Yu, C.H.; Polishchuk, R.; Dmitriev, O.Y.; Lutsenko, S. Molecular events initiating exit of a copper-transporting ATPase ATP7B from the trans-Golgi network. J. Biol. Chem. 2012, 287, 36041–36050. [Google Scholar] [CrossRef] [Green Version]
- La Fontaine, S.; Ackland, M.L.; Mercer, J.F. Mammalian copper-transporting P-type ATPases, ATP7A and ATP7B: Emerging roles. Int. J. Biochem. Cell. Biol. 2010, 42, 206–209. [Google Scholar] [CrossRef] [Green Version]
- Shanmugavel, K.P.; Wittung-Stafshede, P. Copper relay path through the N-terminus of Wilson disease protein, ATP7B. Metallomics 2019, 1, 1472–1480. [Google Scholar] [CrossRef] [Green Version]
- Fanni, D.; Pilloni, L.; Orrù, S.; Coni, P.; Liguori, C.; Serra, S.; Lai, M.L.; Uccheddu, A.; Contu, L.; Van Eyken, P.; et al. Expression of ATP7B in normal human liver. Eur. J. Histochem. 2005, 49, 371–378. [Google Scholar] [CrossRef] [Green Version]
- Chang, I.J.; Hahn, S.H. The genetics of Wilson disease. Handb. Clin. Neurol. 2017, 142, 19–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hamza, I.; Faisst, A.; Prohaska, J.; Chen, J.; Gruss, P.; Gitlin, J.D. The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis. Proc. Natl. Acad. Sci. USA 2001, 98, 6848–6852. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shanmugavel, K.P.; Kumar, R.; Li, Y.; Wittung-Stafshede, P. Wilson disease missense mutations in ATP7B affect metal-binding domain structural dynamics. Biometals 2019, 32, 875–885. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Bie, P.; Muller, P.; Wijmenga, C.; Klomp, L.W. Molecular pathogenesis of Wilson and Menkes disease: Correlation of mutations with molecular defects and disease phenotypes. J. Med. Genet. 2007, 44, 673–688. [Google Scholar] [CrossRef] [Green Version]
- Weiss, K.H.; Schilsky, M. Wilson Disease. In GeneReviews® [Internet]; Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Amemiya, A., Eds.; University of Washington: Seattle, WA, USA. Available online: https://www.ncbi.nlm.nih.gov/sites/books/NBK1512/ (accessed on 1 January 2023).
- Poon, K.S.; Teo, Z.H.; Yap, J.H.; Koay, E.S.; Tan, K. Challenges in molecular diagnosis of Wilson disease: Viewpoint from the clinical laboratory. J. Clin. Pathol. 2020, 73, 231–234. [Google Scholar] [CrossRef]
- Sanchez-Monteagudo, A.; Alvarez-Sauco, M.; Sastre, I.; Martinez-Torres, I.; Lupo, V.; Berenguer, M.; Espinos, C. Genetics of Wilson disease and Wilson-like phenotype in a clinical series from eastern Spain. Clin. Genet. 2020, 97, 758–763. [Google Scholar] [CrossRef]
- Chen, H.I.; Jagadeesh, K.A.; Birgmeier, J.; Wenger, A.M.; Guturu, H.; Schelley, S.; Bernstein, J.A.; Bejerano, G. An MTF1 binding site disrupted by a homozygous variant in the promoter of ATP7B likely causes Wilson Disease. Eur. J. Hum. Genet. 2018, 26, 1810–1818. [Google Scholar] [CrossRef] [Green Version]
- Todorov, T.; Balakrishnan, P.; Savov, A.; Socha, P.; Schmidt, H.H. Intragenic Deletions in ATP7B as an Unusual Molecular Genetics Mechanism of Wilson’s Disease Pathogenesis. PLoS ONE 2016, 11, e0168372. [Google Scholar] [CrossRef] [Green Version]
- Sánchez-Monteagudo, A.; Ripollés, E.; Berenguer, M.; Espinós, C. Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease. Biomedicines 2021, 9, 1100. [Google Scholar] [CrossRef]
- Stapelbroek, J.M.; Bollen, C.W.; van Amstel, J.K.; van Erpecum, K.J.; van Hattum, J.; van den Berg, L.H.; Klomp, L.W.; Houwen, R.H. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: Results of a meta-analysis. J. Hepatol. 2004, 41, 758–763. [Google Scholar] [CrossRef]
- Gu, Y.H.; Kodama, H.; Du, S.L.; Gu, Q.J.; Sun, H.J.; Ushijima, H. Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese. Han and Hui ethnic patients with Wilson’s disease. Clin. Genet. 2003, 64, 479–484. [Google Scholar] [CrossRef] [PubMed]
- Abdelghaffar, T.Y.; Elsayed, S.M.; Elsobky, E.; Bochow, B.; Büttner, J.; Schmidt, H. Mutational analysis of ATP7B gene in Egyptian children with Wilson disease: 12 novel mutations. J. Hum. Genet. 2008, 53, 681. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gojova, L.; Jansova, E.; Kulm, M.; Pouchla, S.; Kozak, L. Genotyping microarray as a novel approach for the detection of ATP7B gene mutations in patients with Wilson disease. Clin. Genet. 2008, 73, 441–452. [Google Scholar] [CrossRef]
- Jang, J.H.; Lee, T.; Bang, S.; Kim, Y.E.; Cho, E.H. Carrier frequency of Wilson’s disease in the Korean population: A DNA-based approach. J. Hum. Genet. 2017, 62, 815–818. [Google Scholar] [CrossRef]
- Xu, A.; Lv, T.; Zhang, B.; Zhang, W.; Ou, X.; Huang, J. Development and evaluation of an unlabeled probe high-resolution melting assay for detection of ATP7B mutations in Wilson’s disease. J. Clin. Lab. Anal. 2017, 31, e22064. [Google Scholar] [CrossRef]
- Gromadzka, G.; Schmidt, H.H.; Genschel, J.; Bochow, B.; Rodo, M.; Tarnacka, B.; Litwin, T.; Chabik, G.; Członkowska, A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson’s disease. Clin. Gen. 2005, 68, 524–532. [Google Scholar] [CrossRef] [PubMed]
- Vrabelova, S.; Letocha, O.; Borsky, M.; Kozak, L. Mutation analysis of the ATP7B gene.and genotype/phenotype correlation in 227 patients with Wilson disease. Mol. Genet. Metab. 2005, 86, 277–285. [Google Scholar] [CrossRef] [PubMed]
- Al Jumah, M.; Majumdar, R.; Al Rajeh, S.; Awada, A.; Al Zaben, A.; Al Traif, I.; Al Jumah, A.R.; Rehana, Z. A clinical and genetic study of 56 Saudi Wilson disease patients: Identification of Saudi-specific mutations. Eur. J. Neurol. 2004, 11, 121–124. [Google Scholar] [CrossRef]
- Salman, H.M.; Amin, M.; Syed, J.; Sarfraz, Z.; Sarfraz, A.; Sarfraz, M.; Farfán Bajaña, M.J.; Felix, M.; Cherrez-Ojeda, I. Biochemical testing for the diagnosis of Wilson’s disease: A systematic review. J. Clin. Lab. Anal. 2022, 36, e24191. [Google Scholar] [CrossRef]
- Knoppers, B.M. Genetic information and the family: Are we our brother’s keeper? Trends Biotechnol. 2002, 20, 85–86. [Google Scholar] [CrossRef] [PubMed]
- European Parliament; Rothley, W.; Casini, C. Ethical and Legal Problems of Genetic Engineering and Human Artificial Insemination; EU Publications Office: Luxembourg, 1990. [Google Scholar]
- Mukherjee, S.; Dutta, S.; Majumdar, S.; Biswas, T.; Jaiswal, P.; Sengupta, M. Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation. Park. Relat. Disord. 2014, 20, 75–81. [Google Scholar] [CrossRef] [PubMed]
- Jónsson, H.; Sulem, P.; Kehr, B.; Kristmundsdottir, S.; Zink, F.; Hjartarson, E.; Hardarson, M.T.; Hjorleifsson, K.E.; Eggertsson, H.P.; Gudjonsson, S.A.; et al. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature 2017, 549, 519–522. [Google Scholar] [CrossRef] [PubMed]
- Kerkar, N.; Rana, A. Wilson Disease in Children. Clin. Liver Dis. 2022, 26, 473–488. [Google Scholar] [CrossRef] [PubMed]
- Członkowska, A.; Gromadzka, G.; Chabik, G. Monozygotic female twins discordant for phenotype of Wilson’s disease. Mov. Disord. 2009, 24, 1066–1069. [Google Scholar] [CrossRef] [PubMed]
- Dzieżyc, K.; Litwin, T.; Chabik, G.; Gramza, K.; Członkowska, A. Families with Wilson’s disease in subsequent generations: Clinical and genetic analysis. Mov. Disord. 2014, 29, 1828–1832. [Google Scholar] [CrossRef]
- Członkowska, A.; Rodo, M.; Gromadzka, G. Late onset Wilson’s disease: Therapeutic implications. Mov. Disord. 2008, 23, 896–898. [Google Scholar] [CrossRef]
- Forbes, J.R.; Cox, D.W. Functional Characterization of Missense Mutations in ATP7B: Wilson Disease Mutation or Normal Variant? Am. J. Hum. Genet. 1998, 63, 1663–1674. [Google Scholar] [CrossRef] [Green Version]
- Papur, O.S.; Terzioglu, O.; Koc, A. Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model. J. Trace Elem. Med. Biol. 2015, 31, 33–36. [Google Scholar] [CrossRef] [Green Version]
- Chandhok, G.; Horvath, J.; Aggarwal, A.; Bhatt, M.; Zibert, A.; Schmidt, H.H. Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines. World J. Gastroenterol. 2016, 22, 4109–4119. [Google Scholar] [CrossRef]
- Betts, M.J.; Russell, R.B. Amino acid properties and consequences of substitutions. In Bioinformatics for Geneticists; Wiley: Hoboken, NJ, USA, 2003. [Google Scholar] [CrossRef]
- Ng, P.C.; Henikoff, S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003, 31, 3812–3814. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Staiger, D.; Brown, J.W. Alternative splicing at the intersection of biological timing, development, and stress responses. Plant Cell. 2013, 25, 3640–3656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thusberg, J.; Olatubosun, A.; Vihinen, M. Performance of mutation pathogenicity prediction methods on missense variants. Hum. Mutat. 2011, 32, 358–368. [Google Scholar] [CrossRef] [PubMed]
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cox, D.W.; Fraser, F.C.; Sass-Kortsak, A. A genetic study of Wilson’s disease: Evidence for heterogeneity. Am. J. Hum. Genet. 1972, 24, 646–666. [Google Scholar] [PubMed]
- Hofer, H.; Willheim-Polli, C.; Knoflach, P.; Gabriel, C.; Vogel, W.; Trauner, M.; Müller, T.; Ferenci, P. Identification of a novel Wilson disease gene mutation frequent in Upper Austria: A genetic and clinical study. J. Hum. Genet. 2012, 57, 564–567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hou, H.; Chen, D.; Liu, J.; Feng, L.; Zhang, J.; Liang, X.; Xu, Y.; Li, X. Clinical and Genetic Analysis in Neurological Wilson’s Disease Patients with Neurological Worsening Following Chelator Therapy. Front. Genet. 2022, 13, 875694. [Google Scholar] [CrossRef]
- Panagiotakaki, E.; Tzetis, M.; Manolaki, N.; Loudianos, G.; Papatheodorou, A.; Manesis, E.; Nousia-Arvanitakis, S.; Syropioulou, V.; Kanavakis, E. Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B). Am. J. Med. Genet. 2004, 131, 168–173. [Google Scholar] [CrossRef]
- Palsson, R.; Jonasson, J.G.; Kristjansson, M.; Bodvarsson, A.; Goldin, R.D.; Cox, D.W.; Olafsson, S. Genotype-phenotype interactions in Wilson’s disease: Insight from an Icelandic mutation. Eur. J. Gastroenterol. Hepatol. 2001, 13, 433–436. [Google Scholar] [CrossRef]
- Okada, T.; Shiono, Y.; Hayashi, H.; Satoh, H.; Sawada, T.; Suzuki, A.; Takeda, Y.; Yano, M.; Michitaka, K.; Onji, M.; et al. Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson’s disease. Hum. Mutat. 2000, 15, 454–462. [Google Scholar] [CrossRef]
- Angius, A.; Dessi, V.; Lovicu, M.; De Virgiliis, S.; Pirastu, M.; Cao, A. Early and severe neurological features in a Wilson disease patient compound heterozygous for two frameshift mutations. Eur. J. Pediatr. 1998, 157, 128–129. [Google Scholar] [CrossRef] [PubMed]
- Wu, Z.Y.; Wang, N.; Lin, M.T.; Fang, L.; Murong, S.X.; Yu, L. Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in Chinese patients with Wilson disease. Arch. Neurol. 2001, 58, 971–976. [Google Scholar] [CrossRef] [Green Version]
- Loudianos, G.; Dessi, V.; Lovicu, M.; Angius, A.; Altuntas, B.; Giacchino, R.; Marazzi, M.; Marcellini, M.; Sartorelli, M.R.; Sturniolo, G.C.; et al. Mutation analysis in patients of Mediterranean descent with Wilson disease: Identification of 19 novel mutations. J. Med. Genet. 1999, 36, 833–836. [Google Scholar] [PubMed]
- Tomić, A.; Dobricić, V.; Novaković, I.; Svetel, M.; Pekmezović, T.; Kresojević, N.; Potrebić, A.; Kostić, V.S. Mutational analysis of ATP7B gene and the genotype-phenotype correlation in patients with Wilson’s disease in Serbia. Vojnosanit Pregl. 2013, 70, 457–462. [Google Scholar] [CrossRef]
- Ferenci, P. Phenotype-genotype correlations in patients with Wilson’s disease. Ann. N. Y. Acad. Sci. 2014, 1315, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Deguti, M.M.; Genschel, J.; Cancado, E.L.; Barbosa, E.R.; Bochow, B.; Mucenic, M.; Porta, G.; Lochs, H.; Carrilho, F.J.; Schmidt, H.H. Wilson disease: Novel mutations in the ATP7B gene and clinical correlation in Brazilian patients. Hum. Mutat. 2004, 23, 398–407. [Google Scholar] [CrossRef]
- Tsivkovskii, R.; Efremov, R.G.; Lutsenko, S. The role of the invariant His-1069 in folding and function of the Wilson’s disease protein, the human copper-transporting ATPase ATP7B. J. Biol. Chem. 2003, 278, 13302–13308. [Google Scholar] [CrossRef] [Green Version]
- Payne, A.S.; Kelly, E.J.; Gitlin, J.D. Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation. Proc. Natl. Acad. Sci. USA 1998, 95, 10854–10859. [Google Scholar] [CrossRef] [Green Version]
- Iida, M.; Terada, K.; Sambongi, Y.; Wakabayashi, T.; Miura, N.; Koyama, K.; Futai, M.; Sugiyama, T. Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae. FEBS Lett. 1998, 428, 281–285. [Google Scholar] [CrossRef] [Green Version]
- Gromadzka, G.; Schmidt, H.H.; Genschel, J.; Bochow, B.; Rodo, M.; Tarnacka, B.; Litwin, T.; Chabik, G.; Członkowska, H. 1069Q mutation in ATP7B and biochemical parameters of copper metabolism and clinical manifestation of Wilson’s disease. Mov. Disord. 2006, 21, 245–248. [Google Scholar] [CrossRef]
- Cocos, R.; Sendroiu, A.; Schipor, S.; Bohîlţea, L.C.; Şendroiu, I.; Raicu, F. Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson’s disease: Genetic and clinical homogeneity. PLoS ONE 2014, 9, e98520. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Villarreal, L.; Daniels, S.; Shaw, S.H.; Cotton, D.; Galvin, M.; Geskes, J.; Bauer, P.; Sierra-Hernandez, A.; Buckler, A.; Tugores, A. High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): A genetic and clinical study. Hepatology 2000, 32, 1329–1336. [Google Scholar] [CrossRef] [PubMed]
- Ferenci, P.; Stremmel, W.; Czlonkowska, A.; Szalay, F.; Viveiros, A.; Stättermayer, A.F.; Bruha, R.; Houwen, R.; Pop, T.L.; Stauber, R.; et al. Age, sex, but not ATP7B genotype effectively influences the clinical phenotype of Wilson disease. Hepatology 2014, 26, 49–56. [Google Scholar] [CrossRef]
- Firneisz, G.; Szonyi, L.; Ferenci, P.; Gorog, D.; Nemes, B.; Szalay, F. Wilson disease in two consecutive generations: An exceptional family. Am. J. Gastroenterol. 2001, 96, 2269–2271. [Google Scholar] [CrossRef] [PubMed]
- Mihaylova, V.; Todorov, T.; Jelev, H.; Kotsev, I.; Angelova, L.; Kosseva, O.; Georgiev, G.; Ganeva, R.; Cherninkova, S.; Tankova, L.; et al. Neurological symptoms, genotype-phenotype correlations and ethnic-specific differences in Bulgarian patients with Wilson disease. Neurologist 2012, 18, 184–189. [Google Scholar] [CrossRef]
- Medici, V.; LaSalle, J.M. Genetics and epigenetic factors of Wilson disease. Ann. Transl. Med. 2019, 7, 58. [Google Scholar] [CrossRef]
- Dedoussis, G.V.; Genschel, J.; Sialvera, T.E.; Bochow, B.; Manolaki, N.; Manios, Y.; Tsafantakis, E.; Schmidt, H. Wilson disease: High prevalence in a mountainous area of Crete. Ann. Hum. Genet. 2005, 69, 268–274. [Google Scholar] [CrossRef]
- Coffey, A.J.; Durkie, M.; Hague, S.; McLay, K.; Emmerson, J.; Lo, C.; Klaffke, S.; Joyce, C.J.; Dhawan, A.; Hadzic, N.; et al. A genetic study of Wilson’s disease in the United Kingdom. Brain 2013, 136, 1476–1487. [Google Scholar] [CrossRef] [Green Version]
- Scheinberg, I.H. Penicillamine in Wilson’s disease. Lancet 1982, 1, 1469. [Google Scholar] [CrossRef]
- Yu, M.; Ren, L.; Zheng, M.; Hong, M.; Wei, Z. Delayed Diagnosis of Wilson’s Disease Report From 179 Newly Diagnosed Cases in China. Front. Neurol. 2022, 13, 884840. [Google Scholar] [CrossRef]
- Saito, T. An assessment of efficiency in potential screening for Wilson’s disease. J. Epidemiol. Community Health 1981, 35, 274–280. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parkes, D. Wilson’s disease. Br. Med. J. Clin. Res. Ed. 1984, 288, 1180–1181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wallace, D.F.; Dooley, J.S. ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease. Hum. Genet. 2020, 139, 1065–1075. [Google Scholar] [CrossRef] [PubMed]
- Roy, S.; McCann, C.J.; Ralle, M.; Ray, K.; Ray, J.; Lutsenko, S.; Jayakanthan, S. Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties. Sci. Rep. 2020, 10, 13487. [Google Scholar] [CrossRef]
- Das, S.K.; Ray, K. Wilson’s disease: An update. Nat. Clin. Pract. Neurol. 2006, 2, 482–493. [Google Scholar] [CrossRef]
- Cartwright, G.E.; Markowitz, H.; Shields, G.S.; Wintrobe, M.M. Studies on copper metabolism. XXIX. A. Critical analysis of serum copper and CP concentrations in normal subjects, patients with Wilson’s disease and relatives of patients with Wilson’s disease. Am. J. Med. 1960, 28, 555–563. [Google Scholar] [CrossRef]
- Heuyer, G.; Baudoin, A.; Azima, H. Considerations on Wilson’s disease; genealogic, clinical, and metabolic investigations on 60 members of one family. Rev. Neurol. 1953, 89, 165–181. [Google Scholar]
- Neale, F.C.; Fischer-Williams, M. Copper metabolism in normal adults and in clinically normal relatives of patients with Wilson’s disease. J. Clin. Pathol. 1958, 11, 441–447. [Google Scholar] [CrossRef] [Green Version]
- Sternlieb, I.; Morell, A.G.; Bauer, C.D.; Combes, B.; De Bobes-Sternberg, S. Schein-Berg, I.H. Detection of the heterozygous carrier of the Wilson’s disease gene. J. Clin. Investig. 1961, 40, 707–715. [Google Scholar] [CrossRef]
- Haghighat, M.; Dehghani, S.M.; Imanieh, M.H.; Gholami, S. Determination of liver enzymes, serum CP and urine copper in parents of children with Wilson’s disease. Saudi Med. J. 2009, 29, 1056–1057. [Google Scholar]
- Tórsdóttir, G.; Gudmundsson, G.; Kristinsson, J.; Snaedal, J.; Jóhannesson, T. CP and superoxide dismutase (SOD1) in heterozygotes for Wilson disease: A case control study. Neuropsychiatr. Dis. Treat. 2009, 5, 55–59. [Google Scholar] [CrossRef] [Green Version]
- Gromadzka, G.; Chabik, G.; Mendel, T.; Wierzchowska, A.; Rudnicka, M.; Czlonkowska, A. Middle-aged heterozygous carriers of Wilson’s disease do not present with significant phenotypic deviations related to copper metabolism. J. Genet. 2010, 89, 463–467. [Google Scholar] [CrossRef] [PubMed]
- Gromadzka, G.; Członkowska, A. Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on the age at onset of neuropsychiatric symptoms in Wilson’s disease. Int. J. Neurosci. 2011, 121, 8–15. [Google Scholar] [CrossRef] [PubMed]
- Gromadzka, G.; Kruszyńska, M.; Wierzbicka, D.; Litwin, T.; Dzieżyc, K.; Wierzchowska-Ciok, A.; Chabik, G.; Członkowska, A. Gene variants encoding proteins involved in antioxidant defense system and the clinical expression of Wilson disease. Liver Int. 2015, 35, 215–222. [Google Scholar] [CrossRef]
- Gromadzka, G.; Rudnicka, M.; Chabik, G.; Przybyłkowski, A.; Członkowska, A. Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson’s disease. J. Hepatol. 2011, 55, 913–919. [Google Scholar] [CrossRef] [PubMed]
- Litwin, T.; Gromadzka, G.; Członkowska, A. Apolipoprotein E gene (APOE) genotype in Wilson’s disease: Impact on clinical presentation. Park. Relat. Disord. 2012, 18, 367–369. [Google Scholar] [CrossRef] [PubMed]
- Kocabay, G.; Tutuncu, Y.; Yilmaz, H.; Demir, K. Impact of apolipoprotein E genotypes on phenotypic expression in Turkish patients with Wilson’s disease. Scand. J. Gastroenterol. 2009, 44, 1270–1271. [Google Scholar] [CrossRef] [PubMed]
- Gu, Y.H.; Kodama, H.; Du, S.L. Apolipoprotein E genotype analysis in Chinese Han ethnic children with Wilson’s disease, with a concentration on those homozygous for R778L. Brain Dev. 2005, 27, 551–553. [Google Scholar] [CrossRef]
- Wang, X.P.; Wang, X.H.; Bao, Y.C.; Zhou, J.N. Apolipoprotein E genotypes in Chinese patients with Wilson’s disease. QJM 2003, 96, 541–542. [Google Scholar] [CrossRef] [Green Version]
- Zhou, D.; Jia, S.; Yi, L.; Wu, Z.; Song, Y.; Zhang, B.; Li, Y.; Yang, X.; Xu, A.; Li, X.; et al. Identification of potential modifier genes in Chinese patients with Wilson disease. Metallomics 2022, 14, mfac024. [Google Scholar] [CrossRef]
- Merle, U.; Stremmel, W.; Gessner, R. Influence of homozygosity for methionine at codon 129 of the human prion gene on the onset of neurological and hepatic symptoms in Wilson disease. Arch. Neurol. 2006, 63, 982–985. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Przybylkowski, A.; Gromadzka, G.; Czlonkowska, A. Polymorphisms of metal transporter genes DMT1 and ATP7A in Wilson’s disease. J. Trace Elem. Med. Biol. 2014, 28, 8–12. [Google Scholar] [CrossRef] [PubMed]
- Weiss, K.H.; Runz, H.; Noe, B.; Gotthardt, D.N.; Merle, U.; Ferenci, P.; Stremmel, W.; Fullekrug, J. Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease. J. Inherit. Metab. Dis. 2010, 33, 233–240. [Google Scholar] [CrossRef] [PubMed]
- Bost, M.; Piguet-Lacroix, G.; Parant, F.; Wilson, C.M. Molecular analysis of Wilson patients: Direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis. J. Trace Elem. Med. Biol. 2012, 26, 97–101. [Google Scholar] [CrossRef]
- Penning, L.C.; Berenguer, M.; Czlonkowska, A.; Double, K.L.; Dusek, P.; Espinós, C.; Lutsenko, S.; Medici, V.; Papenthin, W.; Stremmel, W.; et al. A Century of Progress on Wilson Disease and the Enduring Challenges of Genetics, Diagnosis, and Treatment. Biomedicines 2023, 11, 420. [Google Scholar] [CrossRef]
- Stattermayer, A.F.; Traussnigg, S.; Dienes, H.P.; Aigner, E.; Stauber, R.; Lackner, K.; Hofer, H.; Stift, J.; Wrba, F.; Stadlmayr, A.; et al. Hepatic steatosis in Wilson disease--Role of copper and PNPLA3 mutations. J. Hepatol. 2015, 63, 156–163. [Google Scholar] [CrossRef]
- Xu, R.; Tao, A.; Zhang, S.; Deng, Y.; Chen, G. Association between patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and nonalcoholic fatty liver disease: A HuGE review and meta-analysis. Sci. Rep. 2015, 5, 9284. [Google Scholar] [CrossRef] [Green Version]
- Vigano, M.; Valenti, L.; Lampertico, P.; Facchetti, F.; Motta, B.M.; D’Ambrosio, R.; Romagnoli, S.; Dongiovanni, P.; Donati, B.; Fargion, S.; et al. Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B. Hepatology 2013, 58, 1245–1252. [Google Scholar] [CrossRef]
- Kluska, A.; Kulecka, M.; Litwin, T.; Dziezyc, K.; Balabas, A.; Piatkowska, M.; Paziewska, A.; Dabrowska, M.; Mikula, M.; Kaminska, D.; et al. Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson’s disease phenotype. Liver. Int. 2019, 39, 177–186. [Google Scholar] [CrossRef] [Green Version]
- Mordaunt, C.E.; Kieffer, D.A.; Shibata, N.M.; Czlonkowska, A. Epigenomic signatures in liver and blood of Wilson disease patients include hypermethylation of liver-specific enhancers. Epigenetics Chromatin 2019, 12, 10. [Google Scholar] [CrossRef]
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Gromadzka, G.; Bendykowska, M.; Przybyłkowski, A. Wilson’s Disease—Genetic Puzzles with Diagnostic Implications. Diagnostics 2023, 13, 1287. https://doi.org/10.3390/diagnostics13071287
Gromadzka G, Bendykowska M, Przybyłkowski A. Wilson’s Disease—Genetic Puzzles with Diagnostic Implications. Diagnostics. 2023; 13(7):1287. https://doi.org/10.3390/diagnostics13071287
Chicago/Turabian StyleGromadzka, Grażyna, Maria Bendykowska, and Adam Przybyłkowski. 2023. "Wilson’s Disease—Genetic Puzzles with Diagnostic Implications" Diagnostics 13, no. 7: 1287. https://doi.org/10.3390/diagnostics13071287