OMIA:000667-9615 : Mucopolysaccharidosis VII in Canis lupus familiaris (dog)

In other species: domestic cat

Categories: Lysosomal storage disease

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 253220 (trait) , 611499 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1998

Cross-species summary: Mucopolysaccharidosis VII is a lysosomal storage disease in which there is a buildup (storage) of mucopolysaccharides (glycosaminoglycans), due to the lack of the lysosomal enzyme acid hydrolase beta-glucuronidase (EC 3.2.1.31).

Species-specific description: Mucopolysaccharidosis VII is a lysosomal storage disease characterized by accumulation of undegraded glycosaminoglycans (dermatan, heparan, and chondroitin sulfates) in lysosomes. Clinical signs include facial dysmorphia, diffuse corneal clouding, appendicular and axial skeletal lesions, and glycosaminoglycans in urine. Affected animals are deficient in the enzyme beta-glucuronidase, which is a lysosomal acid hydrolase. Affected animals have very low enzyme activity compared to normal animals, and carriers have 40-60% enzyme activity compared to normal animals. The mode of inheritance is autosomal recessive. The causative mutation is a G to A substitution in the gene coding for the hydrolase, beta-glucuronidase (GUSB). There is a test available to detect the causative mutation. Testing siblings of affected dogs is recommended. Breeding of carriers or affected dogs is not recommended. Edited by Mark Haskins, VMD, Ph.D

Mapping: By conducting a GWAS on 7 affected and 11 control Brazilian Terriers, each genotyped with the Illumina’s 22K SNP chip (yielding 16,595 SNPs for analysis), Hytönen et al. (2012) highlighted a region on chromosome CFA6. Subsequent homozygosity mapping narrowed the region to 13Mb, including more than 200 genes. [FN; 20 May 2013]

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans and other mammals), Ray et al. (1998; Genomics 48:248-253) identified the initial causative mutation as a "guanosine to adenine base change at nucleotide position 559 in the canine cDNA sequence [that] causes an arginine to histidine substitution at amino acid position 166" of the gene coding for hydrolase beta-glucuronidase (GUSB). In Brazilian Terriers, Hytönen et al. (2012) sequenced the entire 13Mb candidate region from their GWAS (see Mapping section), and discovered that the disorder in this breed is due to a "missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB)".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: At 4 weeks of age, affected dogs show a shortened, broad face, low-set ears, and a laterally broad chest. By 8 weeks of age, diffuse corneal clouding is apparent. At 9 weeks of age, affected dogs are half as large as their normal littermates, but have disproportionately large heads. Polymorphonuclear leukocytes and lymphocytes from affected animals contain coarse cytoplasmic granules that stain with toluidine blue. Urine from affected animals contain excessive chondroitin 4- and 6-sulfates and dermatan and heparan sulfates. By 2 to 5 months of age, affected dogs have trouble standing but can move in sternal recumbency. Most joints are easily subluxated and crepitant, with swollen, fluctuant joint capsules filled with excessive synovial fluid. There is significant epiphyseal dysplasia. Cardiac abnormalities, primarily mitral insufficiency and aortic aneurism can be present but are variable (Haskins et al., 1991).

Pathology: Affected animals are deficient in the enzyme beta-glucuronidase, which is a lysosomal acid hydrolase. Affected animals have very low enzyme activity compared to normal animals, and carriers have 40-60% enzyme activity compared to normal animals. Signs are caused by accumulation of undegraded glycosaminoglycans in lysosomes (Ray et al., 1999). Affected animals exhibit a misshapen and narrowed trachea, thickening of the AV heart valve leaflets and chordae tendinae, thickened aortic arch, hyperplasia of synovial membranes, and erosion of the articular cartilage (Haskins et al., 1991). Cytoplasmic vacuoles are evident in neurons of the central nervous system, hepatocytes, Kupffer cells, keratocytes, retinal pigment epithelium, AV heart valve fibroblasts, aortic smooth muscle cells, leukocytes, chondrocytes, and synovial cells. These vacuoles are either empty or contain granular or lamellar material (Haskins et al., 1991).

Control: Testing siblings of affected dogs is recommended. Breeding of carriers or affected dogs is not recommended.

Genetic testing: There is a test available to detect the causative mutation.

Breeds: Brazilian Terrier (Dog) (VBO_0200231), German Shepherd Dog (Dog) (VBO_0200577).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GUSB glucuronidase, beta Canis lupus familiaris 6 NC_051810.1 (548724..535764) GUSB Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
58 Brazilian Terrier (Dog) Mucopolysaccharidosis VII GUSB missense Naturally occurring variant CanFam3.1 6 g.740428G>A c.866C>T p.(P289L) 2012 22815736 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
57 German Shepherd Dog (Dog) Mucopolysaccharidosis VII GUSB missense Naturally occurring variant CanFam3.1 6 g.741429C>T c.497G>A p.(R166H) ROS_Cfam_1.0:g.546709C>T ENSCAFT00845023689.1:c.482G>A ENSCAFP00845018598.1:p.Arg161His rs1152388412 rs1152388412 1998 9521879 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2021). OMIA:000667-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Gawri, R., Lau, Y.K., Lin, G., Shetye, S.S., Zhang, C., Jiang, Z., Abdoun, K., Scanzello, C.R., Jo, S.Y., Mai, W., Dodge, G.R., Casal, M.L., Smith, L.J. :
Dose-dependent effects of enzyme replacement therapy on skeletal disease progression in mucopolysaccharidosis VII dogs. Mol Ther Methods Clin Dev 28:12-26, 2023. Pubmed reference: 36570425. DOI: 10.1016/j.omtm.2022.11.006.
2021 Corda, E., Swenson, C.L., Scott, M.A., Sledge, D.G., Fyfe, J.C. :
Blood and bone marrow findings in two pups with mucopolysaccharidosis type VII. Vet Clin Pathol 50:164-169, 2021. Pubmed reference: 33719080. DOI: 10.1111/vcp.12963.
Peck, S.H., Lau, Y.K., Kang, J.L., Lin, M., Arginteanu, T., Matalon, D.R., Bendigo, J.R., O'Donnell, P., Haskins, M.E., Casal, M.L., Smith, L.J. :
Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity. Mol Genet Metab , 2021. Pubmed reference: 34154922. DOI: 10.1016/j.ymgme.2021.06.005.
2020 Story, B.D., Miller, M.E., Bradbury, A.M., Million, E.D., Duan, D., Taghian, T., Faissler, D., Fernau, D., Beecy, S.J., Gray-Edwards, H.L. :
Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80, 2020. Pubmed reference: 32219101. DOI: 10.3389/fvets.2020.00080.
Switonski, M. :
Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222. DOI: 10.1007/s13353-020-00554-8.
2019 Kantaputra, P.N., Smith, L.J., Casal, M.L., Kuptanon, C., Chang, Y.C., Nampoothiri, S., Paiyarom, A., Veerasakulwong, T., Trachoo, O., Ketudat Cairns, J.R., Chinadet, W., Tanpaiboon, P. :
Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII. Am J Med Genet A 179:486-493, 2019. Pubmed reference: 30653816. DOI: 10.1002/ajmg.a.61034.
Peck, S.H., Tobias, J.W., Shore, E.M., Malhotra, N.R., Haskins, M.E., Casal, M.L., Smith, L.J. :
Molecular profiling of failed endochondral ossification in mucopolysaccharidosis VII. Bone 128:115042, 2019. Pubmed reference: 31442675. DOI: 10.1016/j.bone.2019.115042.
2016 Gurda, B.L., De Guilhem De Lataillade, A., Bell, P., Zhu, Y., Yu, H., Wang, P., Bagel, J., Vite, C.H., Sikora, T., Hinderer, C., Calcedo, R., Yox, A.D., Steet, R.A., Ruane, T., O'Donnell, P., Gao, G., Wilson, J.M., Casal, M., Ponder, K.P., Haskins, M.E. :
Evaluation of AAV-mediated gene therapy for central nervous system disease in canine mucopolysaccharidosis VII. Mol Ther 24:206-16, 2016. Pubmed reference: 26447927. DOI: 10.1038/mt.2015.189.
2015 Peck, S.H., O'Donnell, P.J., Kang, J.L., Malhotra, N.R., Dodge, G.R., Pacifici, M., Shore, E.M., Haskins, M.E., Smith, L.J. :
Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs. Mol Genet Metab 116:195-203, 2015. Pubmed reference: 26422116. DOI: 10.1016/j.ymgme.2015.09.008.
2014 Serratrice, N., Cubizolle, A., Ibanes, S., Mestre-Francés, N., Bayo-Puxan, N., Creyssels, S., Gennetier, A., Bernex, F., Verdier, J.M., Haskins, M.E., Couderc, G., Malecaze, F., Kalatzis, V., Kremer, E.J. :
Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector. J Control Release 181C:22-31, 2014. Pubmed reference: 24607662. DOI: 10.1016/j.jconrel.2014.02.022.
2013 Bigg, P.W., Baldo, G., Sleeper, M.M., O'Donnell, P.A., Bai, H., Rokkam, V.R., Liu, Y., Wu, S., Giugliani, R., Casal, M.L., Haskins, M.E., Ponder, K.P. :
Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs. Mol Genet Metab 110:319-28, 2013. Pubmed reference: 23856419. DOI: 10.1016/j.ymgme.2013.06.013.
Bigg, P.W., Sleeper, M.M., O'Donnell, P.A., Liu, Y., Wu, S., Casal, M.L., Haskins, M.E., Ponder, K.P. :
The effect of neonatal gene therapy with a gamma retroviral vector on cardiac valve disease in mucopolysaccharidosis VII dogs after a decade. Mol Genet Metab 110:311-8, 2013. Pubmed reference: 23860311. DOI: 10.1016/j.ymgme.2013.06.015.
Broeckx, B.J., Coopman, F., Verhoeven, G.E., Van Haeringen, W., van de Goor, L., Bosmans, T., Gielen, I., Saunders, J.H., Soetaert, S.S., Van Bree, H., Van Neste, C., Van Nieuwerburgh, F., Van Ryssen, B., Verelst, E., Van Steendam, K., Deforce, D. :
The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany. PLoS One 8:e74811, 2013. Pubmed reference: 24069350. DOI: 10.1371/journal.pone.0074811.
Cubizolle, A., Serratrice, N., Skander, N., Colle, M.A., Ibanes, S., Gennetier, A., Bayo-Puxan, N., Mazouni, K., Mennechet, F., Joussemet, B., Cherel, Y., Lajat, Y., Vite, C., Bernex, F., Kalatzis, V., Haskins, M.E., Kremer, E.J. :
Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain. Mol Ther , 2013. Pubmed reference: 24343103. DOI: 10.1038/mt.2013.283.
Xing, E.M., Knox, V.W., O'Donnell, P.A., Sikura, T., Liu, Y., Wu, S., Casal, M.L., Haskins, M.E., Ponder, K.P. :
The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade. Mol Genet Metab 109:183-93, 2013. Pubmed reference: 23628461. DOI: 10.1016/j.ymgme.2013.03.013.
2012 Hytönen, M.K., Arumilli, M., Lappalainen, A.K., Kallio, H., Snellman, M., Sainio, K., Lohi, H. :
A novel GUSB mutation in Brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis VII. PLoS One 7:e40281, 2012. Pubmed reference: 22815736. DOI: 10.1371/journal.pone.0040281.
Sewell, A.C., Haskins, M.E., Giger, U. :
Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats. Vet Clin Pathol 41:548-57, 2012. Pubmed reference: 23121383. DOI: 10.1111/j.1939-165x.2012.00485.x.
Smith, L.J., Martin, J.T., O'Donnell, P., Wang, P., Elliott, D.M., Haskins, M.E., Ponder, K.P. :
Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs. Mol Genet Metab 107:145-52, 2012. Pubmed reference: 22510705. DOI: 10.1016/j.ymgme.2012.03.013.
Smith, L.J., Baldo, G., Wu, S., Liu, Y., Whyte, M.P., Giugliani, R., Elliott, D.M., Haskins, M.E., Ponder, K.P. :
Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII. Mol Genet Metab 107:153-60, 2012. Pubmed reference: 22513347. DOI: 10.1016/j.ymgme.2012.03.014.
2010 Hordeaux, J., Deniaud, J., Bemelmans, I., Bertrand, L., Moreau, S., Amiaud, J., Wyers, M., Cherel, Y., Colle, MA. :
Histopathologic Changes of the Ear in Canine Models of Mucopolysaccharidosis Types I and VII. Vet Pathol , 2010. Pubmed reference: 20930106. DOI: 10.1177/0300985810384413.
Metcalf, JA., Linders, B., Wu, S., Bigg, P., O'Donnell, P., Sleeper, MM., Whyte, MP., Haskins, M., Ponder, KP. :
Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII dogs may be due to increased cytokine expression. Mol Genet Metab 99:396-407, 2010. Pubmed reference: 20044292. DOI: 10.1016/j.ymgme.2009.12.003.
Smith, LJ., Martin, JT., Szczesny, SE., Ponder, KP., Haskins, ME., Elliott, DM. :
Altered lumbar spine structure, biochemistry, and biomechanical properties in a canine model of mucopolysaccharidosis type VII. J Orthop Res 28:616-22, 2010. Pubmed reference: 19918911. DOI: 10.1002/jor.21030.
2008 Herati, RS., Knox, VW., O'Donnell, P., D'Angelo, M., Haskins, ME., Ponder, KP. :
Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy. Mol Genet Metab 95:142-51, 2008. Pubmed reference: 18707908. DOI: 10.1016/j.ymgme.2008.07.003.
2007 Walton, RM., Wolfe, JH. :
Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease. J Neuropathol Exp Neurol 66:760-9, 2007. Pubmed reference: 17882020. DOI: 10.1097/nen.0b013e31812571c8.
2006 Wang, B., O'Malley, TM., Xu, L., Vite, C., Wang, P., O'Donnell, PA., Ellinwood, NM., Haskins, ME., Ponder, KP. :
Expression in blood cells may contribute to biochemical and pathological improvements after neonatal intravenous gene therapy for mucopolysaccharidosis VII in dogs. Mol Genet Metab 87:8-21, 2006. Pubmed reference: 16275036. DOI: 10.1016/j.ymgme.2005.08.014.
2004 Mango, RL., Xu, L., Sands, MS., Vogler, C., Seiler, G., Schwarz, T., Haskins, ME., Ponder, KP. :
Neonatal retroviral vector-mediated hepatic gene therapy reduces bone, joint, and cartilage disease in mucopolysaccharidosis VII mice and dogs. Mol Genet Metab 82:4-19, 2004. Pubmed reference: 15110316. DOI: 10.1016/j.ymgme.2004.01.015.
Silverstein Dombrowski, DC., Carmichael, KP., Wang, P., O'Malley, TM., Haskins, ME., Giger, U. :
Mucopolysaccharidosis type VII in a German Shepherd Dog. J Am Vet Med Assoc 224:553-7, 532-3, 2004. Pubmed reference: 14989549.
Sleeper, MM., Fornasari, B., Ellinwood, NM., Weil, MA., Melniczek, J., O'Malley, TM., Sammarco, CD., Xu, L., Ponder, KP., Haskins, ME. :
Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII. Circulation 110:815-20, 2004. Pubmed reference: 15289379. DOI: 10.1161/01.CIR.0000138747.82487.4B.
2002 Ponder, K.P., Melniczek, J.R., Xu, L.F., Weil, M.A., O'Malley, T.M., O'Donnell, P.A., Knox, V.W., Aguirre, G.D., Mazrier, H., Ellinwood, N.M., Sleeper, M., Maguire, A.M., Volk, S.W., Mango, R.L., Zweigle, J., Wolfe, J.H., Haskins, M.E. :
Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs Proceedings of the National Academy of Sciences of the United States of America 99:13102-13107, 2002. Pubmed reference: 12232044. DOI: 10.1073/pnas.192353499.
Xu, L., Haskins, M.E., Melniczek, J.R., Gao, C., Weil, M.A., O'Malley, T.M., O'Donnell, P.A., Mazrier, H., Ellinwood, N.M., Zweigle, J., Wolfe, J.H., Ponder, K.P. :
Transduction of hepatocytes after neonatal delivery of a Moloney murine leukemia virus based retroviral vector results in long-term expression of beta-glucuronidase in mucopolysaccharidosis VII dogs. Mol Ther 5:141-53, 2002. Pubmed reference: 11829521. DOI: 10.1006/mthe.2002.0527.
2000 Sammarco, C., Weil, M., Just, C., Weimelt, S., Hasson, C., O'Malley, T., Evans, S.M., Wang, P., Casal, M.L., Wolfe, J., Haskins, M. :
Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII Bone Marrow Transplantation 25:1289-1297, 2000. Pubmed reference: 10871735. DOI: 10.1038/sj.bmt.1702448.
1999 Ray, J., Scarpino, V., Laing, C., Haskins, M.E. :
Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII Journal of Heredity 90:119-123, 1999. Pubmed reference: 9987917.
1998 Ray, J., Haskins, M.E., Ray, K. :
Molecular diagnostic tests for ascertainment of genotype at the mucopolysaccharidosis type VII locus in dogs American Journal of Veterinary Research 59:1092-1095, 1998. Pubmed reference: 9736382.
Ray, J., Bouvet, A., Desanto, C., Fyfe, J.C., Xu, D.B., Wolfe, J.H., Aguirre, G.D., Patterson, D.F., Haskins, M.E., Henthorn, P.S. :
Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells Genomics 48:248-253, 1998. Pubmed reference: 9521879. DOI: 10.1006/geno.1997.5189.
1996 Mollard, R.J., Telegan, P., Haskins, M., Aguirre, G. :
Corneal endothelium in mucopolysaccharide storage disorders. Morphologic studies in animal models. Cornea 15:25-34, 1996. Pubmed reference: 8907377.
1994 Sheridan, O., Wortman, J., Harvey, C., Hayden, J., Haskins, M. :
Craniofacial abnormalities in animal models of mucopolysaccharidoses I, VI, and VII. J Craniofac Genet Dev Biol 14:7-15, 1994. Pubmed reference: 8006122.
1992 Haskins, M.E., Otis, E.J., Hayden, J.E., Jezyk, P.F., Stramm, L. :
Hepatic Storage of Glycosaminoglycans in Feline and Canine Models of Mucopolysaccharidose-I, Mucopolysaccharidose-VI, and Mucopolysaccharidose-VII Veterinary Pathology 29:112-119, 1992. Pubmed reference: 1632054.
1991 Haskins, M.E., Aguirre, G.D., Jezyk, P.F., Schuchman, E.H., Desnick, R.J., Patterson, D.F. :
Mucopolysaccharidosis Type-VII (Sly Syndrome) - Beta- Glucuronidase-Deficient Mucopolysaccharidosis in the Dog American Journal of Pathology 138:1553-1555, 1991. Pubmed reference: 1905109.
1990 Stramm, L.E., Wolfe, J.H., Schuchman, E.H., Haskins, M.E., Patterson, D.F., Aguirre, G.D. :
Beta-glucuronidase mediated pathway essential for retinal pigment epithelial degradation of glycosaminoglycans. Disease expression and in vitro disease correction using retroviral mediated cDNA transfer. Exp Eye Res 50:521-32, 1990. Pubmed reference: 2164946.
Wolfe, J.H., Schuchman, E.H., Stramm, L.E., Concaugh, E.A., Haskins, M.E., Aguirre, G.D., Patterson, D.F., Desnick, R.J., Gilboa, E. :
Restoration of Normal Lysosomal Function in Mucopolysaccharidosis Type-VII Cells by Retroviral Vector- Mediated Gene Transfer Proceedings of the National Academy of Sciences of the United States of America 87:2877-2881, 1990. Pubmed reference: 2158095.
1989 Schuchman, E.H., Toroyan, T.K., Haskins, M.E., Desnick, R.J. :
Characterization of the Defective Beta-Glucuronidase Activity in Canine Mucopolysaccharidosis Type-VII Enzyme 42:174-180, 1989. Pubmed reference: 2515056.
1984 Haskins, M.E., Desnick, R.J., DiFerrante, N., Jezyk, P.F., Patterson, D.F. :
Beta-glucuronidase deficiency in a dog: a model of human mucoploysaccharidosis VII Pediatric Research 18:980-984, 1984. Pubmed reference: 6436780.

Edit History


  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Martha MaloneyHuss on 17 Aug 2011
  • Changed by Vicki Meyers-Wallen on 18 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 18 Jul 2012
  • Changed by Frank Nicholas on 04 Sep 2012
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Frank Nicholas on 27 Aug 2016
  • Changed by Imke Tammen2 on 25 Jun 2021
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  • Changed by Imke Tammen2 on 30 Aug 2021