Hypohidrotic ectodermal dysplasia (HAD), X-linked (EDA-related)

 

Gene: EDA

Transmission: Chromosome X, recessive or dominant

Mutations:

HED1 (Deutsche Holstein cattle): Deletion, EDA gene: c.397_502 del, p.(Met133Val frameshift STOP 111), deletion exon3, Chr.X.

HED2 (Deutsche Holstein cattle): Substitution, EDA gene: c.924+2T>G, intron8-9, Chr.X.

HED3 (Angus-Charlais-Simmental cross): Substitution, EDA gene: c.730C>T, p.(Arg244STOP), exon5, Chr.X.

HED4 (Holstein): Deletion, EDA gene: c.48_66 del., p.(Ala16_Ser22 del, frameshift, STOP 55), exon1, Chr.X.

HED5 (Holstein): Substitution, EDA gene: c.802C>A, skipping of exon8 with frameshift STOP, Chr.X.

HED6 (Holstein): Insertion, EDA gene: LINE1 insertion between exon1 and exon2, frameshift, premature STOP in exon2.

HED7 (Japanese Black): Insertion, EDA gene: c.280_281 ins AGGG, p.(Gly94Gln frameshift STOP 49), exon1, Chr.X.

HED8 (Holstein): inversion, EDA gene: 3.8Mb chromosomal inversion in Chr.X involving EDA gene.

HED9 (Angus-Simmental cross): Deletion, EDA gene: 53Kb deletion including exons 3 to 8.

HED10 (British Blue-Holstein cross): Deletion, EDA gene: c.397_502 del, p.(Met133Val frameshift STOP 111), Chr.X.

HED11 (Limousin): Substitution, EDA gene: c.881A>G, p.(Glu294Gly), exon7, Chr.X.

Medical system: Dermal, dental, respiratory

Breeds: Holstein, Japanese black, Limousin, crosses

Age of onset of symptoms: At birth.

Hypohidrotic ectodermal dysplasia (HED) is a congenital condition seen in a number of mammalian species involving developmental anomalies of ectodermal derived structures.  Typically, this involves reduced number of sweat glands (hypohidrosis), reduced hair (hypotrichosis), and reduced or absent teeth (oligodentia).  In humans, HED can be caused by mutations in the EDA gene, which codes for the ectodysplasin A protein.  The ectodysplasin A protein is involved in embryonic cell signalling and is important for the development of ectoderm derived structures such as hair, ectodermal derived glands and teeth.  The EDA gene is located on the X chromosome, such that HED displays sex linked inheritance, and mostly affects male animals.

HED has been diagnosed sporadically in a number of cattle breeds, either in single animals or in limited pedigrees.  Clinically, reduced hair and teeth are seen in the newborn animal.  The calf can suffer from bronchopneumonia due to an absence of branchial glands.  Molecular characterisation of HED cases in cattle reveal a range of mutations in the X-chromosome linked EDA gene, from single nucleotide polymorphisms (SNPs) to small or large deletions to LINE insertions to chromosomal inversions.  Because HED is sex linked and affected animals are easily identified at a young age, the occasional de novo mutations that occur in the EDA gene that give rise to HED have little chance of breed penetration. Thus, although HED may be observed occasionally it should not cause undue concern to cattle breeders and veterinarians.

 

References:

OMIA link: [0543-9913]

Krull F, Bleyer M, Schäfer J, Brenig B. (2024) A missense mutation in the highly conserved TNF-like domain of Ectodysplasin A is the candidate causative variant for X-linked hypohidrotic ectodermal dysplasia in Limousin cattle: Clinical, histological, and molecular analyses. PLoS One 19:e0291411. [pm/38252617]

Drögemüller C, Distl O, Leeb T. (2001) Partial deletion of the bovine ED1 gene causes anhidrotic ectodermal dysplasia in cattle.  Genome Research 11:1699-1705. [pm/11591646]

With contributions by: Daphné Dubé and Justine Gauthier, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).