OMIA:001805-9615 : Amelogenesis imperfecta, ENAM-related in Canis lupus familiaris
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 204650 (trait) , 104500 (trait) , 606585 (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: 2013
Species-specific description: Also known as Enamel hypoplasia.
Mapping: After genotyping each of 22 affected and 49 normal Italian Grehounds with the Illumina CanineHD Genotyping BeadChip, which contains 173,662 SNPs, Gandolfi et al. (2013) conducted a GWAS which mapped the disorder to a 1.84 Mb region of chromosome CFA15, which contains 10 genes.
Molecular basis: Three of the ten genes in the candidate region described in the Mapping section above are involved in enamel development. Mutations in one of these three positional candidate genes (ENAM) are causal in one form of human amelogenesis imperfecta. Gandolfi et al. (2013) therefore chose to sequence the canine ENAM gene in three affecteds and one normal Italian Greyhound. Sequencing revealed the likely causal mutation as "a 5-bp deletion . . . , c.1991_1995delTTTCC, in exon 10, resulting in a frameshift and premature termination codon at position 668 (p.Phe665Argfs*3) of the protein".
In Samoyed dogs, Pedersen et al. (2017) reported "Two potential deleterious mutations in SCL24A on CFA8 and in strong linkage disequilibrium were ultimately identified in ARAI affected dogs, an asynonymous change (C to T) in exon 12 changing amino acid proline to leucine and a 21 bp duplication in exon 17". The extent to which either of these variants is actually associated with the disorder in this breed is not clear from the paper: the missense variant was not investigated beyond its discovery, and for the deletion variant, Pedersen et al. (2017) reported that "The 14/182 (7.8%) dogs that were presumed to have enamel hypoplasia based on physical examination and DNA testing all were homozygous for the mutation. Twenty of 168 (12%) heathy dogs were found to be heterologous [sic] for the mutation and most were parents or known close relatives of affected dogs." Thus it is not evident whether all dogs diagnosed solely on a clinical basis were homozygous and whether all known parents of affected dogs were heterozygous.
Hytönen et al. (2019) reported a likely causal variant in Parson Russell Terriers: "A fully segregating missense variant (c.716C>T) in exon 8 of ENAM substitutes a well-conserved proline to leucine, p.(Pro239Leu), resulting in a clinical hypomineralization of teeth".
Clinical features: For Italian Greyhounds, the clinical signs as reported by Gandolfi et al. (2013) are "A brownish mottling and roughening of teeth is apparent in areas where enamel is thin or absent . . . . Affected permanent teeth are often small and pointed compared with normal teeth . . . . Greater than normal gaps between teeth are often noticeable in young dogs and become more apparent with age due to premature enamel wear".
Prevalence: Hytönen et al. (2019) reported a carrier frequency of 9% for the c.716C>T ENAM variant in Parson Russell Terriers.
Breeds: Greyhound, Parson Russell Terrier, Standard Poodle.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ENAM||enamelin||Canis lupus familiaris||13||NC_051817.1 (60739886..60753519)||ENAM||Homologene, Ensembl , NCBI gene|
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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|
|1044||Parson Russell Terrier||Amelogenesis imperfecta||ENAM||missense||Naturally occurring variant||CanFam3.1||13||g.59945218C>T||c.716C>T||p.(P239L)||XM_539305.4; XP_539305.3||2019||30877375||Genomic coordinates in CanFam3.1 provided by Robert Kuhn and Zoe Shmidt.|
|452||Italian Greyhound||Amelogenesis imperfecta||ENAM||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||13||g.59946493_59946497del||c.1991_1995delTTTCC||p.(F665Rfs*3)||XM_539305.4; XP_539305.3; published as c.1991_1995delTTTCC||2013||23638899||Genomic coordinates in CanFam3.1 provided by Robert Kuhn|
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.
|2019||Hytönen, M.K., Arumilli, M., Sarkiala, E., Nieminen, P., Lohi, H. :|
|Canine models of human amelogenesis imperfecta: identification of novel recessive ENAM and ACP4 variants. Hum Genet 138:525-533, 2019. Pubmed reference: 30877375 . DOI: 10.1007/s00439-019-01997-8.|
|2018||Nicholas, F.W., Mellersh, C., Lewis, T. :|
|Letter to the editor regarding an autosomal recessive mutation in SCL24A4 causing enamel hypoplasia in Samoyed and its relationship to breed-wide genetic diversity. Canine Genet Epidemiol 5:4, 2018. Pubmed reference: 29744112 . DOI: 10.1186/s40575-018-0059-7.|
|2017||Pedersen, N.C., Shope, B., Liu, H. :|
|An autosomal recessive mutation in SCL24A4 causing enamel hypoplasia in Samoyed and its relationship to breed-wide genetic diversity. Canine Genet Epidemiol 4:11, 2017. Pubmed reference: 29201383 . DOI: 10.1186/s40575-017-0049-1.|
|2013||Gandolfi, B., Liu, H., Griffioen, L., Pedersen, N.C. :|
|Simple recessive mutation in ENAM is associated with amelogenesis imperfecta in Italian Greyhounds. Anim Genet 44:569-78, 2013. Pubmed reference: 23638899 . DOI: 10.1111/age.12043.|
|2009||Mannerfelt, T., Lindgren, I. :|
|Enamel defects in Standard Poodle dogs in Sweden. Journal of Veterinary Dentistry 26:213-215, 2009.|
- Created by Frank Nicholas on 13 May 2013
- Changed by Frank Nicholas on 13 May 2013
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