OMIA 001805-9615 : Amelogenesis imperfecta, ENAM-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 204650 , 104500

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[4] 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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ENAM enamelin Canis lupus familiaris 13 NC_006595.3 (59934299..59948279) ENAM Homologene, Ensembl, NCBI gene


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
Italian Greyhound Amelogenesis imperfecta ENAM deletion, small (<=20) c.1991_1995delTTTCC p.Phe665Argfs*3 2013 23638899
Parson Russell Terrier Amelogenesis imperfecta ENAM missense CanFam3.1 13 c.716C>T p.Pro239Leu 2019 30877375


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 :, 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.

Edit History

  • Created by Frank Nicholas on 13 May 2013
  • Changed by Frank Nicholas on 13 May 2013
  • Changed by Frank Nicholas on 21 Jan 2018
  • Changed by Frank Nicholas on 01 Feb 2018
  • Changed by Frank Nicholas on 20 Mar 2019