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Independent DSG4 frameshift variants in cats with hair shaft dystrophy
- Source :
- Molecular Genetics and Genomics, Kiener, Sarah; Rostaher, Ana; Rüfenacht, Silvia; Jagannathan, Vidhya; Sundberg, John P.; Welle, Monika; Leeb, Tosso (2022). Independent DSG4 frameshift variants in cats with hair shaft dystrophy. Molecular genetics and genomics : MGG, 297(1), pp. 147-154. Springer 10.1007/s00438-021-01842-6
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Investigations of hereditary phenotypes in spontaneous mutants may help to better understand the physiological functions of the altered genes. We investigated two unrelated domestic shorthair cats with bulbous swellings of the hair shafts. The clinical, histopathological, and ultrastructural features were similar to those in mice with lanceolate hair phenotype caused by loss-of-function variants in Dsg4 encoding desmoglein 4. We 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. Together with the knowledge on the effects of DSG4 variants in other species, our data suggest that the identified DSG4 variants cause the hair shaft dystrophy. To the best of our knowledge, this study represents the first report of pathogenic DSG4 variants in domestic animals.
- Subjects :
- 10253 Department of Small Animals
610 Medicine & health
Dermatology
Lanceolate
Cat Diseases
030207 dermatology & venereal diseases
03 medical and health sciences
0302 clinical medicine
1311 Genetics
1312 Molecular Biology
Genetics
Animals
Felis catus
Genodermatosis
Animal Fur
Frameshift Mutation
Molecular Biology
Skin
030304 developmental biology
Whole-genome sequencing
0303 health sciences
Base Sequence
Whole Genome Sequencing
630 Agriculture
integumentary system
Homozygote
Hair shaft dysplasia
Alopecia
General Medicine
Codon, Nonsense
Case-Control Studies
Cats
590 Animals (Zoology)
570 Life sciences
biology
Original Article
Desmogleins
Hair Diseases
Hair Follicle
Subjects
Details
- ISSN :
- 16174623 and 16174615
- Volume :
- 297
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Genomics
- Accession number :
- edsair.doi.dedup.....8d58959b9d3671a5aa1cf33bc7df8930