OMIA:002452-9685 : Hair shaft dysplasia, DSG4-related in Felis catus
Categories: Integument (skin) phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2021
History: The phenotype has been termed hair shaft dysplasia or hair shaft dystrophy by different pathologists.
Molecular basis: Kiener et al. (2022) investigated two unrelated domestic shorthair cats with partial alopecia and bulbous swellings of the hair shafts. Based on the striking phenotype resembling lanceolate mice, the authors focused their analysis on DSG4 encoding desmoglein 4 as the top functional candidate gene. The authors "sequenced the genomes from both affected cats and compared the data of each affected cat to 61 control genomes. A search for private homozygous variants in the DSG4 candidate gene revealed independent frameshift variants in each case, c.76del or p.Ile26fsLeu*4 in case no. 1 and c.1777del or p.His593Thrfs*23 in case no. 2. DSG4 is a transmembrane glycoprotein located primarily in the extracellular part of desmosomes, a complex of adhesion molecules responsible for connecting the keratin intermediate filaments of neighbouring epithelial cells. Desmosomes are essential for normal hair shaft formation. Both identified DSG4 variants in the affected cats lead to premature stop codons and truncate major parts of the open-reading frame. We assume that this leads to a complete loss of DSG4 function, resulting in an incorrect formation of the desmosomes and causing the development of defective hair shafts." (Kiener et al., 2022).
Clinical features: Rostaher et al. (2021) described the clinical and histopathological phenotype in two out of four affected siblings in a litter of domestic shorthair cats. "Both cats presented with extensive alopecia of the dorsal thorax, plantar and palmar surfaces of the limbs, convex pinnae and most of the face. The cats were multicoloured and neither had alopecia associated with a specific coat colour. In addition to the affected truncal hairs, the vibrissae were short and broken. Macroscopic evaluation of the skin surface revealed many short, broken hair shafts, some of which had club or lance-head shaped ends. In addition to the unremarkable general physical examination, the nails, teeth, eyes and skin texture were unaffected." (Rostaher et al., 2021)
Figure 2 of Kiener et al. (2022) compared the phenotypes of the original litter identified by Rostaher et al. (2021) and an unrelated case with an independent DSG4 variant. All investigated cats shared similar clinical features comprising partial alopecia and the presence of characteristic lance-shaped hair tips.
Pathology: "Light and scanning electron microscopy of the hairs revealed lance- or spear-head shaped defects of the hair tip. Histological findings were swollen hair shafts, initially above the hair bulb matrix and later found in the distal parts of the telogen hair follicles, similar to those observed in Dsg4^lahJ Krt75^tm1Der mutant mice. Transmission electron microscopy of the hair shaft and hair follicles showed a loss in the normal structure of the guard hairs in the alopecic cats. There was a statistically significant decrease in sulfur content just below the defects in the hair shafts (trichothiodystrophy)." (Rostaher et al., 2021).
Breed: Domestic Shorthair.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|DSG4||desmoglein 4||Felis catus||D3||NC_058379.1 (53088837..53132546)||DSG4||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|
|1392||Domestic Shorthair||Hair shaft dysplasia||DSG4||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||D3||g.55315010del||c.76del||p.(I26Lfs*4)||XM_019815116.1; XP_019670675.1||2022||34878611|
|1393||Domestic Shorthair||Hair shaft dysplasia||DSG4||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||D3||g.55336127del||c.1777del||p.(H593Tfs*23)||XM_019815116.1; XP_019670675.1||2022||34878611|
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.
|2022||Kiener, S., Rostaher, A., Rüfenacht, S., Jagannathan, V., Sundberg, J.P., Welle, M., Leeb, T. :|
|Independent DSG4 frameshift variants in cats with hair shaft dystrophy. Mol Genet Genomics 297:147-154, 2022. Pubmed reference: 34878611 . DOI: 10.1007/s00438-021-01842-6.|
|2021||Rostaher, A., Bettenay, S., Specht, L., Silva, K.A., Bechtold, L., Chen, J., Majzoub, M., Mueller, R.S., Sundberg, J.P. :|
|Hair follicle dystrophy in a litter of domestic cats resembling lanceolate hair mutant mice. Vet Dermatol 32:74-e14, 2021. Pubmed reference: 33470013 . DOI: 10.1111/vde.12925.|
|2013||Maina, E., Colombo, S., Abramo, F., Pasquinelli, G. :|
|A case of pili torti in a young adult domestic short-haired cat. Vet Dermatol 24:289-e68, 2013. Pubmed reference: 23384010 . DOI: 10.1111/vde.12004.|
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