OMIA:001973-9615 : Ichthyosis, SLC27A4-related in Canis lupus familiaris
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 608649 (trait) , 604194 (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: 2015
Mapping: The disease locus was mapped to chromosome 9 by a genome-wide association study (GWAS) using 9 affected and 13 control dogs and illumina canine_HD SNP chip genotypes (Metzger et al. 2015). The most significantly associated markers were located in the 740 kb interval from 54,031,320 to 54,772,131 (CanFam3.1).
Molecular basis: Metzger et al. (2015) identified a single nucleotide sustitution in exon 8, c.1250G>A, as the most likely causative variant. This variant alters the encoded amino acid seqeunce (p.Arg417Gln). However, the variant predominantly leads to aberrant splicing as it generates a cryptic splice acceptor site within exon 8. Metzger et al. (2015) identified a transcript lacking 54 nucleotides from the beginning of exon 8 in affected dogs. Western blot analysis demonstrated that the SLC27A4 protein is only expressed at very low levels in the skin of affected dogs compared to control dogs.
Clinical features: Clinical examination revealed signs of a generalized severe hyperkeratosis in all cases with a formation of a strongly wrinkled, thickened and scaling skin especially in the region of the eyes and nose. These changes led to a dry inelastic and lichenified skin of an untidy appearance in the affected dogs and a markedly swollen periocular skin which impeded the opening of the puppy’s eyes in some cases. In-between the wrinkles the exudative character of the skin promoted secondary infections. Due to the poor prognosis, all affected dogs were euthanized at the age of 7–40 days. Additional computer tomographic and endoscopic examinations after euthanasia in two five week old affected dogs revealed a ventrally displaced auditory canal with an atypically wrinkled shape but no signs of other anomalies (Metzger et al. 2015).
Pathology: Affected Great Dane puppies had epidermal and follicular orthokeratotic hyperkeratosis, enlarged keratohyaline granules, vacuolated keratinocytes, and accumulations of an eosinophilic and alcianophilic, lipid-rich material within dilated hair follicular lumina and the cytoplasm of sebocytes. The macroscopic, histopathologic, and ultrastructural skin changes indicated a new variant of a primary disorder of cornification with congenital, non-epidermolytic, lamellar ichthyosiform appearance (Hoffmann et al. 2016)
Breed: Great Dane.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SLC27A4||solute carrier family 27 (fatty acid transporter), member 4||Canis lupus familiaris||9||NC_051813.1 (56099730..56084580)||SLC27A4||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|
|937||Great Dane||Ichthyosis, SLC27A4-related||SLC27A4||splicing||Naturally occurring variant||CanFam3.1||9||g.55168916C>T||c.1250G>A||XM_548438.6; XP_548438.3; cDNA sequencing confirmed that a "new acceptor site is created by the A-allele ... that results in a shorter RNA product. ... affected dogs show aberrantly spliced transcript with an in-frame loss of the first 54 bp of exon 8" (Metzger et al., 2015)||2015||26506231||Genomic position in CanFam3.1 provided by Robert Kuhn and Mateo Etcheveste.|
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.
|2021||Mauldin, E.A., Elias, P.M. :|
|Ichthyosis and hereditary cornification disorders in dogs. Vet Dermatol 32:567-e154, 2021. Pubmed reference: 34796560 . DOI: 10.1111/vde.13033.|
|2016||Hoffmann, A., Metzger, J., Wöhlke, A., Peters, M., Junginger, J., Mischke, R., Distl, O., Hewicker-Trautwein, M. :|
|Congenital ichthyosis in 14 Great Dane puppies with a new presentation. Vet Pathol 53:614-20, 2016. Pubmed reference: 26242581 . DOI: 10.1177/0300985815595516.|
|2015||Metzger, J., Wöhlke, A., Mischke, R., Hoffmann, A., Hewicker-Trautwein, M., Küch, E.M., Naim, H.Y., Distl, O. :|
|A novel SLC27A4 splice acceptor site mutation in Great Danes with ichthyosis. PLoS One 10:e0141514, 2015. Pubmed reference: 26506231 . DOI: 10.1371/journal.pone.0141514.|
- Created by Tosso Leeb on 23 Dec 2015
- Changed by Tosso Leeb on 23 Dec 2015
- Changed by Frank Nicholas on 22 Apr 2016