A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia

Abstract

In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial alopecia, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental X-raying and histopathological findings were consistent with an ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A gene (CM000039.3:g.54509504delT, PRJEB27789). Sanger sequencing of further family members confirmed the PRJEB27789-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 Dachshunds from all other breeds and samples from 34 dog breeds revealed the PRJEB27789 variant to be private for this family. Two heterozygous females showed very mild alopecia but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the PRJEB27789-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.

Lack of airway submucosal glands impairs respiratory host defenses

“…EDA-KO piglets also lacked hair on their upper and lower eyelids but retained eyelashes ( Figure 2D ). These body hair phenotypes are similar to those reported for other animals with mutations in the ectodysplasin pathway ( Vasiliadis et al, 2019 ; Casal et al, 2005b ).…”

“…There are also variable reports of recurrent respiratory tract infections, asthma-like symptoms, and otitis media ( Dietz et al, 2013 ; Clarke et al, 1987 ; Reed et al, 1970 ; Callea et al, 2013 ; Beahrs et al, 1971 ). EDA mutations in mice, dogs, and cattle cause loss of nasal, submandibular, and submucosal glands, and there are limited reports investigating respiratory symptoms and mucus accumulation ( Jaskoll et al, 2003 ; Azar et al, 2016 ; Casal et al, 2005a ; Seeliger et al, 2005 ; Vasiliadis et al, 2019 ). Reports that EDA mutations can cause a decrease or loss of SMGs and produce lung abnormalities suggest the feasibility of using EDA gene disruptions to develop an animal model without SMGs.…”

X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA

“…The distribution of hypotrichosis differs between calves and dogs in that it is generally more extensive in cattle where it generally affects facial skin, dorsal, lateral and ventral parts the neck and trunk, and the proximal portions of limbs. The distribution of ECTD1 hypotrichosis in dogs tends to be more restricted [ 12 , 37 , 39 , 51 ]. Although no comprehensive assessment of glands was attempted in the current study, mucosal glands were absent in upper and lower portions of the respiratory tract.…”

Genetic analysis of a possible case of canine X‐linked ectodermal dysplasia

“…The former was found in a research colony and derived from an affected male German shepherd (Casal et al 1997, Casal et al 2005b). The latter was found in a same family of Dachshunds and was independently identified by Hadji Rasouliha et al (2018) and Vasiliadis et al (2019). A study of three affected males, two of whom were siblings, demonstrated a splicing defect in the EDA gene at the transcript level, but was unable to identify the causative genomic variant (Waluk et al 2016).…”