Document Type

Article

Publication Date

1-2022

Publication Title

Molecular genetics and genomics : MGG

Keywords

JMG, Alopecia, Animal Fur, Animals, Base Sequence, Case-Control Studies, Cat Diseases, Cats, Codon, Nonsense, Desmogleins, Frameshift Mutation, Hair Diseases, Hair Follicle, Homozygote, Skin, Whole Genome Sequencing

JAX Source

Mol Genet Genomics 2022 Jan; 297(1):147-154

Volume

297

Issue

1

First Page

147

Last Page

154

ISSN

1617-4623

PMID

34878611

DOI

https://doi.org/10.1007/s00438-021-01842-6

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.

Comments

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.

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