ASSOCIATION OF VARIANTS IN THE CP, ATOX1
AND COMMD1 GENES WITH WILSON DISEASE
SYMPTOMS IN LATVIA
Zarina A1,2*, Tolmane I3,4, Krumina Z2, Tutane AI1, Gailite L1
*Corresponding Author: Ms. Agnese Zarina, Scientific Laboratory of Molecular Genetics, Rīga Stradiņš
University, 16 Dzirciema Street, Riga, Latvia, LV-1007. Tel.: +371-6706-1542. Fax: +371-67-471-815.
E-mail: agnese.zarina@rsu.lv or zarina.agnese@gmail.com
page: 37
|
|
CONCLUSIONS
1) The difference variants of the CP gene contribute to
a WD-like phenotype in clinically confirmed WD patients
with neurological symptoms and without pathogenic variants
in the ATP7B gene, but for confirmation, a larger study
group is required; 2) no changes were found in the ATOX1
gene that would cause functional changes of the protein; 3)
no statistically significant differences were found between
allele and genotype frequencies in the COMMD1 gene and
the first clinical manifestations of WD; 4) allelic variants
in the ATOX1 and COMMD1 genes do not modify the
clinical manifestation of WD in Latvian patients.
Declaration of Interest. The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
Funding. This study was partially financed by a grant
of Riga Stradiņš University, Department of Doctoral studies
and grant of Roche Academy.
REFERENCES
1. Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko
S, Medici V, et al. Wilson disease. Nat Rev Dis
Prim. 2018; 4(1): 21.
2. Ala A, Schilsky M. Genetic modifiers of liver injury
in hereditary liver disease. Semin Liver Dis. 2011;
31(2): 208-214.
3. Medici V, Weiss K-H. Genetic and environmental
modifiers of Wilson disease. In: Członkowska A,
Schilsky ML, Editors. Handbook of Clinical Neurology.
Amsterdam, The Netherlands: Elsevier. 2017;
142: 35-41.
4. Kluska A, Kulecka M, Litwin T, Dziezyc K, Balabas
A, Piatkowska M, 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(1): 177-186.
5. Simon I, Schaefer M, Reichert J, Stremmel W. Analysis
of the human Atox 1 homologue in Wilson patients.
World J Gastroenterol. 2008; 14(15): 2383-2387.
6. Gupta A, Chattopadhyay I, Mukherjee S, Sengupta M,
Das SK, Ray K. A novel COMMD1 mutation Thr174
Met associated with elevated urinary copper and signs
of enhanced apoptotic cell death in a Wilson Disease
patient. Behav Brain Funct. 2010; 6: 33.
7. Patel BN, Dunn RJ, Jeong SY, Zhu Q, Julien J-P,
David S. Ceruloplasmin regulates iron levels in the
CNS and prevents free radical injury. J Neurosci.
2002; 22(15): 6578-6586.
8. Zhao N, Xiao J, Zheng Z, Fei G, Zhang F, Jin L, et
al. Single-nucleotide polymorphisms and haplotypes
of non-coding area in the CP gene are correlated with
Parkinson’s disease. Neurosci Bull. 2015; 31(2); 245-
256.
9. Adamsson Eryd S, Sjögren M, Smith JG, Nilsson
PM, Melander O, Hedblad B, et al. Ceruloplasmin
and atrial fibrillation: Evidence of causality from a
population-based Mendelian randomization study. J
Intern Med. 2014; 275(2): 164-171.
10. Arenas de Larriva AP, Norby FL, Chen LY, Soliman
EZ, Hoogeveen RC, Arking DE, et al. Circulating
ceruloplasmin, ceruloplasmin-associated genes, and
the incidence of atrial fibrillation in the atherosclerosis
risk in communities study. Int J Cardiol. 2017;
241: 223-228.
11. Ferenci P, Czlonkowska A, Stremmel W, Houwen
R, Rosenberg W, Schilsky M, et al.; EASL Clinical
Practice Guidelines: Wilson’s disease. J Hepatol.
2012; 56(3): 671-685. 2012. 12. Gromadzka G, Schmidt HHJ, Genschel J, Bochow B,
Rodo M, Tamacka B, et al. 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 Genet. 2005; 68(6): 524-532.
13. Poláková H, Katrincsáková B, Minárik G, Ferakova,
E, Ficek A, Baldovic M, et al. Detection of His-
1069Gln mutation in Wilson disease by bidirectional
PCR amplification of specific alleles (BI-PASA) test.
Gen Physiol Biophys. 2007; 26(2): 91-96.
14. Krumina A, Keiss J, Sondore V, Chernushenko A,
Cernevska G, Zarina A, et al. From clinical and biochemical
to molecular genetic diagnosis of Wilson
disease in Latvia. Genetika. 2008; 44(10): 1379-1384.
15. Zarina A, Tolmane I, Kreile M, Chernushenko A,
Cernevska G, Pukite I, et al. Genetic variation spectrum
in ATP7B gene identified in Latvian patients
with Wilson disease. Mol Genet Genomic Med. 2017;
5(4): 405-409.
16. gnomAD. [Online]. Available: https://gnomad. broadinstitute.
org/. [Accessed: April 15 2019].
17. Chr13: 52.51M-52.51M, 1000 Genomes Browser.
[Online]. Available: https://www.ncbi.nlm.nih.gov/
varia tion/tools/1000genomes/?gts=rs1057516740.
[Accessed: October 16 2018].
18. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-
Foster J, 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(5): 405-424.
19. Human Splicing Finder, Version 3.1. [Online]. Available:
http://www.umd.be/HSF3/. [Accessed: October
18 2018].
20. Hedera P. Update on the clinical management of Wilson’s
disease. Appl Clin Genet. 2017; 10: 9-19.
21. Roberts EA, Schilsky ML. Diagnosis and treatment of
Wilson disease: An update. Hepatology. 2008; 47(6):
2089-2111.
22. Hellman NE, Gitlin JD. Ceruloplasmin metabolism
and function. Annu Rev Nutr. 2002; 22(1): 439-458.
23. van De Sluis B, Rothuizen J, Pearson PL, van Oost
BA, Wijmenga C. Identification of a new copper metabolism
gene by positional cloning in a purebred dog
population. Hum Mol Genet. 2002; 11(2): 165-173.
24. Stuehler B, Reichert J, Stremmel W, Schaefer M.
Analysis of the human homologue of the canine
copper toxicosis gene MURR1 in Wilson disease
patients. J Mol Med. 2004; 82(9): 629-634.
25. Lovicu M, Dessi V, Lepori MB, Zappu A, Zancan
L, Giacchino R, et al.. The canine copper toxicosis
gene MURR1 is not implicated in the pathogenesis
of Wilson disease. J Gastroenterol. 2006; 41(6): 582-
587.
26. Weiss KH, Merle U, Schaefer M, Ferenci P, Fullekrug
J, Stremmel W. Copper toxicosis gene MURR1 is
not changed in Wilson disease patients with normal
blood ceruloplasmin levels. World J Gastroenterol.
2006; 12(14): 2239-2242.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
