A novel mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Holstein cattle

Ogino, Akifumi; Kohama, Namiko; Ishikawa, Shou; Tomita, Keisuke; Nonaka, Sumie; Shimizu, Kazuhiro; Tanabe, Yasutaka; Okawa, Hirokazu; Morita, Mitsuo

doi:10.1111/j.1601-5223.2010.02202.x

Cited by 14 publications

(15 citation statements)

References 16 publications

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“…Clinical and histopathological examinations revealed symptoms similar to those previously reported in EDAR homozygous and EDA hemizygous mutant cattle e.g. [5, 16, 17, 24], thus confirming the diagnosis of HED. In the affected animal, hair follicles were more numerous, thinner and located higher in the dermis of the frontal skin; sebaceous and sweat glands were hypoplastic; teeth were absent with the exception of one malformed premolar on each side of the upper jaw; while horn development appeared normal.…”

Section: Discussionsupporting

confidence: 83%

“…Mutations in EDAR , EDARADD and WNT10A are most frequently autosomal recessive, whereas mutations in EDA, which is located on the X chromosome, are inherited in a X-linked recessive pattern and cause the X-linked form of HED (XLHED) [14]. In contrast to males, females that are heterozygous for EDA mutations typically show less severe symptoms with a reduced degree of hypodontia, mosaic patterns of hypotrichosis, and defective sweat glands along Blaschko’s lines because of random X inactivation [15–17].…”

Section: Introductionmentioning

confidence: 99%

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Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia

et al. 2019

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Background In mammals, hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that is characterized by sparse hair, tooth abnormalities, and defects in cutaneous glands. Only four genes, EDA, EDAR, EDARADD and WNT10A account for more than 90% of HED cases, and EDA, on chromosome X, is involved in 50% of the cases. In this study, we explored an isolated case of a female Holstein calf with symptoms similar to HED. Results Clinical examination confirmed the diagnosis. The affected female showed homogeneous hypotrichosis and oligodontia as previously observed in bovine EDAR homozygous and EDA hemizygous mutants. Under light microscopy, the hair follicles were thinner and located higher in the dermis of the frontal skin in the affected animal than in the control. Moreover, the affected animal showed a five-fold increase in the number of hair follicles and a four-fold decrease in the diameter of the pilary canals. Pedigree analysis revealed that the coefficient of inbreeding of the affected calf (4.58%) was not higher than the average population inbreeding coefficient (4.59%). This animal had ten ancestors in its paternal and maternal lineages. By estimating the number of affected cases that would be expected if any of these common ancestors carried a recessive mutation, we concluded that, if they existed, other cases of HED should have been reported in France, which is not the case. Therefore, we assumed that the causal mutation was dominant and de novo. By analyzing whole-genome sequencing data, we identified a large chromosomal inversion with breakpoints located in the first introns of the EDA and XIST genes. Genotyping by PCR-electrophoresis the case and its parents allowed us to demonstrate the de novo origin of this inversion. Finally, using various sources of information we present a body of evidence that supports the hypothesis that this mutation is responsible for a skewed inactivation of X, and that only the normal X can be inactivated. Conclusions In this article, we report a unique case of X-linked HED affected Holstein female calf with an assumed full inactivation of the normal X-chromosome, thus leading to a severe phenotype similar to that of hemizygous males.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia

et al. 2019

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“…Sequencing and genotyping: PCR amplification of all eight exons and intronic regions flanking exons of the bovine EDA gene was performed using previously published primer sets 5 . The PCR‐amplified fragments were sequenced using the BigDye terminator chemistry v3.1 (Applied Biosystems).…”

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confidence: 99%

De novo mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Japanese Black cattle

et al. 2011

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“…4 B). Six of them were structural variants [ 2 , 20 – 22 , 25 , 26 ] and three involved a single nucleotide [ 16 , 18 , 27 ]. Our study reports a novel, large deletion in EDA and thereby expands the spectrum of causative variants for bovine HED and to emphasize that different loss-of-function mutations in EDA cause a homogenous phenotype.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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A novel mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Holstein cattle

Cited by 14 publications

References 16 publications

Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia

Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia

De novo mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Japanese Black cattle

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

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