Independent DSG4 frameshift variants in cats with hair shaft dystrophy

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Next Generation Sequencing (NGS) Platform
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kiener, Sarah; Jagannathan, Vidya; Welle, Monika Maria and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1617-4615

Publisher:

Springer

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

23 Dec 2021 10:49

Last Modified:

05 Dec 2022 15:55

Publisher DOI:

10.1007/s00438-021-01842-6

PubMed ID:

34878611

BORIS DOI:

10.48350/162079

URI:

https://boris.unibe.ch/id/eprint/162079

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