Hypohidrotic ectodermal dysplasia, X-linked, EDA-related

 

Gene: EDA

Transmission: X-linked, recessive.

For an X-linked recessive genetic disease, a male must have one copy of the mutation in question to be at risk of developing the disease.  All affected males transmit the mutation to all the females of their offspring. A female must have two copies of the mutation in question to be at risk of developing the disease. Females with 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:

German Shepherd mutation: Splicing error, EDA gene; c.910-1 G>A, intron8-9, chromosome X.

Mixed breed mutation: Splicing error, EDA gene; p.(Met129 frameshift STOP 112), deletion of exon2, chromosome X.

Dachshund mutation: Deletion, EDA gene; c.842delT, p.(Leu281His frameshift STOP 22), chromosome X.

Breeds: Dachshund Standard Longhair/Shorthair, German Shepherd, mixed breed

Medical system: Dermal

Age of onset of symptoms: Evident at birth.

X-linked hypohidrotic ectodermal dysplasia (XLHED) in dogs is a genetic disease caused by recessive mutations in the EDA gene, located on the X chromosome. The EDA gene codes for Ectodysplasmin A, a transmembrane protein that plays a signalling role for the embryonic development of ectoderm-derived structures including hair follicles, teeth buds, eccrine sweat glands and sebaceous glands.  Affected animals show signs of alopecia, dental abnormalities, and absence of exocrine glands affecting their tear production and ability to sweat. Additionally, absence of bronchial and tracheal mucous glands predisposes affected individuals to recurrent respiratory infections.  As this disease is sex linked, it is relatively easy to control within a breed.  It acts as a dominant disease in affected males and as a recessive disease in their carrier mothers; affected males are identified by clinical signs while carrier females are identified by having affected male progeny. As such, this disease is of academic interest but not of general concern to breeders.

 

References:

OMIA link: [0543-9615]

Welle MM. (2023) Canine noninflammatory alopecia: An approach to its classification and a diagnostic aid. Vet Pathol 60:748-769. [pm/37191329]

Moura E, Henrique Weber S, Engracia Filho JR, Pimpão CT. (2020) A hypohidrotic ectodermal dysplasia arising from a new mutation in a Yorkshire Terrier dog. Top Companion Anim Med 39:100404. [pm/32482291]

Vasiliadis D, Hewicker-Trautwein M, Klotz D, et al. (2019) A de novo EDA-variant in a litter of shorthaired standard dachshunds with X-linked hypohidrotic ectodermal dysplasia. G3 (Bethesda) 9:95-104. [pm/30397018]

Waluk D, Zur G, Kaufmann R, et al. (2016) A splice defect in the EDA gene in dogs with an X-linked hypohidrotic ectodermal dysplasia (XLHED) phenotype. G3 (Bethesda) 6:2949-2954. [pm/27449516]

Casal ML, Scheidt, JL, Rhodes JL, et al. (2005) Mutation identification in a canine model of X-linked ectodermal dysplasia. Mamm Genome 16:524-3. [pm/16151697]

 

Contributed by: Clarisse Prévost and Arianne Rosseau, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)