OMIA 001443-9940 : Neuronal ceroid lipofuscinosis, 6 in Ovis aries

In other species: dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601780

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2006

Species-specific name: Battens disease

Species-specific symbol: NCL

History: This disorder in sheep was first reported by Jolly and West (1976) and Jolly et al. (1980). Its classification as NCL6 was first reported by Broom et al. (1998).

Mapping: Homozygosity mapping of the Merino disorder enabled Cook et al. (2002) to locate this disorder on chromosome OAR7q13-15. Linkage analysis strongly implicated the CLN6 gene as causing NCL in South Hampshire sheep (Broom et al., 2001), and precluded the CLN6 gene as being related to CLN in the Borderdale breed (Tammen et al., 2006).

Molecular basis: Using the comparative positional candidate gene approach, Tammen et al. (2006) discovered a missense mutation (c.184C>T; p.Arg62Cys)in the CLN6 gene, responsible for NCL6 in Merino sheep.

Mohd Ismail et al. (2012) reported the causal mutation in the South Hampshire breed as a deletion of exon 1 of the CLN6 gene.

Breeds: Merino, South Hampshire.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CLN6 ceroid-lipofuscinosis, neuronal 6, late infantile, variant Ovis aries 7 NC_019464.2 (14832769..14817597) CLN6 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
South Hampshire Neuronal ceroid lipofuscinosis CLN6 deletion, gross (>20) deletion of exon 1 2013 23338040
Merino Neuronal ceroid lipofuscinosis, 6 CLN6 missense c.184C>T p.R62C 2006 17046213

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.
2018 Russell, K.N., Mitchell, N.L., Anderson, N.G., Bunt, C.R., Wellby, M.P., Melzer, T.R., Barrell, G.K., Palmer, D.N. :
Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses. Brain Behav :e01096, 2018. Pubmed reference: 30136763. DOI: 10.1002/brb3.1096.
2016 Cronin, G.M., Beganovic, D.F., Sutton, A.L., Palmer, D., Thomson, P.C., Tammen, I. :
Manifestation of neuronal ceroid lipofuscinosis in Australian Merino sheep: observations on altered behaviour and growth. Appl Anim Behav Sci 175:32-40, 2016. Pubmed reference: 26949278. DOI: 10.1016/j.applanim.2015.11.012.
2015 Palmer, D.N., Neverman, N.J., Chen, J.Z., Chang, C.T., Houweling, P.J., Barry, L.A., Tammen, I., Hughes, S.M., Mitchell, N.L. :
Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network. Biochim Biophys Acta 1852:2279-86, 2015. Pubmed reference: 26073432. DOI: 10.1016/j.bbadis.2015.06.013.
Sawiak, S.J., Perumal, S.R., Rudiger, S.R., Matthews, L., Mitchell, N.L., McLaughlan, C.J., Bawden, C.S., Palmer, D.N., Kuchel, T., Morton, A.J. :
Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging. PLoS One 10:e0132331, 2015. Pubmed reference: 26161747. DOI: 10.1371/journal.pone.0132331.
2014 Grubman, A., Lidgerwood, G.E., Duncan, C., Bica, L., Tan, J.L., Parker, S.J., Caragounis, A., Meyerowitz, J., Volitakis, I., Moujalled, D., Liddell, J.R., Hickey, J.L., Horne, M., Longmuir, S., Koistinaho, J., Donnelly, P.S., Crouch, P.J., Tammen, I., White, A.R., Kanninen, K.M. :
Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder. Acta Neuropathol Commun 2:25, 2014. Pubmed reference: 24581221. DOI: 10.1186/2051-5960-2-25.
2013 Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. :
Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009.
Kanninen, K.M., Grubman, A., Meyerowitz, J., Duncan, C., Tan, J.L., Parker, S.J., Crouch, P.J., Paterson, B.M., Hickey, J.L., Donnelly, P.S., Volitakis, I., Tammen, I., Palmer, D.N., White, A.R. :
Increased zinc and manganese in parallel with neurodegeneration, synaptic protein changes and activation of Akt/GSK3 signaling in ovine CLN6 neuronal ceroid lipofuscinosis. PLoS One 8:e58644, 2013. Pubmed reference: 23516525. DOI: 10.1371/journal.pone.0058644.
Kay, G.W., Palmer, D.N. :
Chronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progression. J Neuroinflammation 10:97, 2013. Pubmed reference: 23899308. DOI: 10.1186/1742-2094-10-97.
2012 Mohd Ismail, I.F., Mitchell, N.L., Hobbs, M., Cavanagh, J.A.L., Palmer, D.N., Tammen, I. :
Next generation sequencing identifies the disease causing mutation for NCL in South Hampshire sheep. 13th International Conference on Neuronal Ceroid Lipofuscinoses (Batten Disease), London, UK :p. 07, 2012.
2008 Oswald, MJ., Palmer, DN., Kay, GW., Barwell, KJ., Cooper, JD. :
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis. Neurobiol Dis 32:50-65, 2008. Pubmed reference: 18634879. DOI: 10.1016/j.nbd.2008.06.004.
2007 Pears, MR., Salek, RM., Palmer, DN., Kay, GW., Mortishire-Smith, RJ., Griffin, JL. :
Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. J Neurosci Res 85:3494-504, 2007. Pubmed reference: 17510975. DOI: 10.1002/jnr.21343.
2006 Tammen, I., Houweling, PJ., Frugier, T., Mitchell, NL., Kay, GW., Cavanagh, JA., Cook, RW., Raadsma, HW., Palmer, DN. :
A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA. Biochim Biophys Acta 1762:898-905, 2006. Pubmed reference: 17046213. DOI: 10.1016/j.bbadis.2006.09.004.
2005 Oswald, MJ., Palmer, DN., Kay, GW., Shemilt, SJ., Rezaie, P., Cooper, JD. :
Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiol Dis 20:49-63, 2005. Pubmed reference: 16137566. DOI: 10.1016/j.nbd.2005.01.025.
2002 Cook, R.W., Jolly, R.D., Palmer, D.N., Tammen, I., Broom, M.F., McKinnon, R. :
Neuronal ceroid lipofuscinosis in Merino sheep Australian Veterinary Journal 80:292-297, 2002. Pubmed reference: 12074311.
2001 Broom, MF., Zhou, C. :
Fine mapping of ovine ceroid lipofuscinosis confirms orthology with CLN6. Eur J Paediatr Neurol 5 Suppl A:33-5, 2001. Pubmed reference: 11589004.
Tammen, I., Cook, RW., Nicholas, FW., Raadsma, HW. :
Neuronal ceroid lipofuscinosis in Australian Merino sheep: a new animal model. Eur J Paediatr Neurol 5 Suppl A:37-41, 2001. Pubmed reference: 11589005.
1999 Broom, MF., Zhou, C., Hill, DF. :
Progress toward positional cloning of ovine neuronal ceroid lipofuscinosis, a model of the human late-infantile variant CLN6. Mol Genet Metab 66:373-5, 1999. Pubmed reference: 10191131. DOI: 10.1006/mgme.1999.2823.
Jolly, R.D., Walkley, S.U. :
Ovine ceroid lipofuscinosis (OCL6): Postulated mechanism of neurodegeneration Molecular Genetics & Metabolism 66:376-380, 1999.
1998 Broom, M.F., Zhou, C.M., Broom, J.E., Barwell, K.J., Jolly, R.D., Hill, D.F. :
Ovine neuronal ceroid lipofuscinosis - a large animal model syntenic with the human neuronal ceroid lipofuscinosis variant CLN6 Journal of Medical Genetics 35:717-721, 1998. Pubmed reference: 9733028.
1992 Goebel, H.H. :
Retina in Various Animal Models of Neuronal Ceroid- Lipofuscinosis American Journal of Medical Genetics 42:605-608, 1992. Pubmed reference: 1609843. DOI: 10.1002/ajmg.1320420435.
1980 Jolly, RD., Janmaat, A., West, DM., Morrison, I. :
Ovine ceroid-lipofuscinosis: a model of Batten's disease. Neuropathol Appl Neurobiol 6:195-209, 1980. Pubmed reference: 6772982.
1976 Jolly, R. D., West, D. M. :
Blindness in South Hampshire sheep: a neuronal ceroid-lipofuscinosis New Zealand Veterinary Journal 24:123, 1976. Pubmed reference: 1067509. DOI: 10.1080/00480169.1976.34298.

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  • Created by Frank Nicholas on 05 Apr 2011
  • Changed by Frank Nicholas on 08 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 20 Aug 2013