A large deletion encompassing exon 2 of the ectodysplasin A (EDA) gene in a British blue crossbred calf with hypohidrotic ectodermal dysplasia

Abstract

Background Hypohidrotic ectodermal dysplasia (HED) is a congenital syndrome of mammals affecting organs and tissues of ectodermal origin characterized by absence or hypoplasia of hair, teeth, and eccrine glands. The disorder has been reported in several species, including humans, mice, dogs and cattle, associated with variants in genes affecting the ectodysplasin pathway, including the X-linked ectodysplasin A (EDA) gene. Until now, nine pathogenic variants have been found in the bovine EDA gene. Here we report a novel variant in EDA in a crossbreed male Belgian Blue calf with HED, and provide an overview of the phenotypic and allelic heterogeneity of EDA-related forms of HED in cattle. Case presentation A 45-day-old male crossbreed British Blue calf was referred with congenital hypotrichosis, oligodontia and omphalitis. On histopathological examination of the nasal planum, nasolabial glands and ducts were not observed. The density of hair follicles was low, and they were small, with a predominance of telogen-phase hairs, and some serocellular crusts. The phenotype of the calf resembled that of HED. Whole-genome sequencing (WGS) was performed and revealed a 21,899 base-pair deletion encompassing the coding exon 2 of EDA, predicted to result in an altered transcript and aberrant protein. Conclusions The clinicopathological and genetic findings were consistent with a case of X-linked HED. A very similar EDA deletion has been previously reported in a family of Holstein cattle with HED. The newly identified hemizygous EDA loss-of-function variant is certainly pathogenic and therefore is the genetic cause for the observed phenotype. This case report provides an additional example of the potential of WGS-based precise diagnostics in livestock species such as cattle to increase the diagnostic yield in rare diseases.

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

“…HED-related malformations do not result in abortion but often cause premature death from inefficient thermoregulation or pneumonia due to decreased pulmonary clearance because the appropriate glands are absent. HED may therefore be considered an indirect lethal factor in cattle [ 15 , 16 ].…”

“…The remaining ten reports relate to XLHED due to EDA mutations, four of which describe small indels [ 5 , 9 , 11 , 14 ]. Another six studies describe structural variations [ 6 , 12 , 13 , 15 – 17 ].…”

“…Affected animals have a sparse, usually lightened coat, malformed or missing teeth, and cannot regulate their body temperature by sweating (hypohidrosis) [1,10]. Calves are characterized by bald patches around the eyes and muzzle and lack teeth with the exception of one malformed caudal molar [11][12][13][14][15]. Mammalian skin is of mesodermal and ectodermal origin and consists of three layers, with the middle layer, the corium, having the most malformed structures.…”

“…To date, there have been 11 reports of HED in cattle, i.e. Red or Black Holstein and various crosses of Red Angus, Charolais, Simmental, Japanese Black or British-blue [3][4][5][6][7][8][9][11][12][13][14][15][16][17]. Penetrance of HED appears to be high and the phenotype is easily observed.…”

Structural Optimization Design of Microfluidic Chips Based on Fast Sequence Pair Algorithm

“…The traditional sequence pair algorithm is a classical layout representation method in the field of electronic design automation. It provides a coding method for the layout scheme of a given device set, which can speed up the enumeration and calculation of layout schemes [ 36 , 37 ].…”