OMIA 001758-9615 : Cataract, early onset in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 116800

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: Primary hereditary cataract

Species-specific symbol: PHC

Inheritance: Barnett (1978) reported single-locus autosomal recessive inheritance.

Mapping: Using sequence data from the initial canine genome assembly (Lindblad-Toh K, Wade CM, Mikkelsen TS et al. Nature 2005; 438: 803–819), Mellersch et al. (2006) identified microsatellite markers "adjacent to and flanking" each of 20 comparative candidate genes (based on known causative mutations in humans and mice). Association analysis with this disorder was conducted within each of the breeds Staffordshire Bull Terriers, American Cocker Spaniels, Golden Retrievers and Miniature Schnauzers. The only association was with markers flanking the gene HSF4 on chromosome CFA5 in Staffordshire Bull Terriers.

Ricketts et al. (2015) mapped a second locus in Australian Shepherd dogs to a 14.16 Mb region on chromosome CFA13 at 46.4 Mb

Molecular basis: Building on their mapping results (see above), Mellersh et al. (2006) sequenced the HSF4 gene in Staffordshire Bull Terriers segregating the disorder, and identified "a single C nucleotide insertion in exon 9 (CFA5 g85286582–85286583insC) that alters the reading frame of the gene and introduces a premature stop codon". The same mutation appears to be causative in Boston Terriers, and a different mutation in the same gene appears to be causative in Australian Shepherds: "a deletion of a C nucleotide at the same position of exon 9 in the affected Australian Shepherds (in which the disorder is autosomal dominant, unlike in the other two breeds, where it is autosomal recessive) (g.85286582delC) . . . , which is also predicted to alter the frame of the gene and introduce a premature stop codon, 177 nucleotides (59 amino acids) further downstream from that introduced by the deletion". Finally, the authors showed that neither of these mutations is causative in American Cocker Spaniels and Golden Retrievers. The following year, Mellersh et al. (2007) showed that late-onset cataract in Boston Terriers is not due to any mutation in HSF4. Engelhardt et al. (2007) showed that HSF4 mutations are not causative for primary cataract in English Cocker Spaniels and Wire-haired Kromfohrlanders. Müller et al. (2008) drew the same conclusion for primary cataract in Dachshunds and Entlebucher Mountain dogs. Mellersh et al. (2009) confirmed the Australian Shepherd mutation but also reported that other mutations are also likely to be involved.

Breeds: Australian Shepherd, Boston Terrier, Staffordshire Bull Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HSF4 heat shock transcription factor 4 Canis lupus familiaris 5 NC_006587.3 (82201224..82190996) HSF4 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.

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
Australian Shepherd Cataract, early onset HSF4 deletion, small (<=20) g.85286582delC 2006 16939467
Staffordshire Bull Terrier Cataract, early onset HSF4 insertion, small (<=20) g.85286582–85286583insC 2006 16939467

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.
2015 Ricketts, S.L., Pettitt, L., McLaughlin, B., Jenkins, C.A., Mellersh, C.S. :
A novel locus on canine chromosome 13 is associated with cataract in the Australian Shepherd breed of domestic dog. Mamm Genome :, 2015. Pubmed reference: 25894238. DOI: 10.1007/s00335-015-9562-2.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
2009 Mellersh, CS., Mclaughlin, B., Ahonen, S., Pettitt, L., Lohi, H., Barnett, KC. :
Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd. Vet Ophthalmol 12:372-8, 2009. Pubmed reference: 19883468. DOI: 10.1111/j.1463-5224.2009.00735.x.
2008 Müller, C., Wöhlke, A., Distl, O. :
Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog. Vet Ophthalmol 11:34-7, 2008. Pubmed reference: 18190350. DOI: 10.1111/j.1463-5224.2007.00598.x.
2007 Engelhardt, A., Wöhlke, A., Distl, O. :
Evaluation of canine heat-shock transcription factor 4 as a candidate for primary cataracts in English Cocker Spaniels and wire-haired Kromfohrlanders. J Anim Breed Genet 124:242-5, 2007. Pubmed reference: 17651328. DOI: 10.1111/j.1439-0388.2007.00663.x.
Mellersh, CS., Graves, KT., Mclaughlin, B., Ennis, RB., Pettitt, L., Vaudin, M., Barnett, KC. :
Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier. J Hered 98:531-3, 2007. Pubmed reference: 17611257. DOI: 10.1093/jhered/esm043.
2006 Mellersh, CS., Pettitt, L., Forman, OP., Vaudin, M., Barnett, KC. :
Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Vet Ophthalmol 9:369-78, 2006. Pubmed reference: 16939467. DOI: 10.1111/j.1463-5224.2006.00496.x.
1978 Barnett, KC. :
Hereditary cataract in the dog. J Small Anim Pract 19:109-20, 1978. Pubmed reference: 642468.
1976 Barnett, K.C. :
Comparative aspects of canine hereditary eye disease. Adv Vet Sci Comp Med 20:39-67, 1976. Pubmed reference: 827198.

Edit History


  • Created by Frank Nicholas on 05 Dec 2012
  • Changed by Frank Nicholas on 05 Dec 2012
  • Changed by Frank Nicholas on 23 Apr 2015