Hair Shaft dysplasia (DSG4-related)

Gene: DSG4

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Mutation 1: Deletion, DSG4 gene: c.76 del.A, p.(Ile26Leu frameshift STOP 4), Chr. D3.

Mutation 2: Deletion, DSG4 gene: c.1777 del.C, p.(His593Thr frameshift STOP 23), Chr.D3.

Medical system: Dermal disorder

Breeds: Domestic Cat shorthair

Age of onset of symptoms: From 3 months to 1.5 years.

Hair shaft dysplasia is a genetic cause of alopecia (lack of hair) and hypotrichosis (reduced hair).  The DSG4 gene codes for the transmembrane protein desmoglein 4 which is integral to the desmosome protein complex found on the surface of epithelial cells.  Keratin intermediate filaments found in the extracellular space are bound to epithelial cells by the desmosome complex, which gives structural integrity to epithelial structures including skin and hair.    Mutations in the DSG4 gene can be responsible for a characteristic “lance tipped” hair shaft defect seen in mouse models of hair shaft dysplasia.

Two separate cases of hair shaft dysplasia in domestic cats were diagnosed clinically, involving partial alopecia, short broken hair shafts, and the lance shaped hair tips as seen in the mouse models. The DSG4 gene was sequenced, and two independent homozygous mutations within the gene were identified and considered responsible for the clinical observations.  Other epithelial structures, such as teeth and nails, were normal.  Neither mutation was seen in 61 control cat genomes that were studied.  The significance of these mutations for the general cat population is not known, and they may well be the result of local but isolated inbreeding hotspots.

References:

OMIA link: [2452-9685]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Kiener S, Rostaher A, Rüfenacht S, et al. (2022) Independent DSG4 frameshift variants in cats with hair shaft dystrophy. Mol Genet Genomics 297:147-154.  [pm/34878611]

Rostaher A, Bettenay S, Specht L, et al. (2021) Hair follicle dystrophy in a litter of domestic cats resembling lanceolate hair mutant mice. Vet Dermatol 32:74-e14.  [pm/33470013]

With contributions by:  Catherine Comeau and Lilou Pitre, Class of 2030, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).