Abstract:BackgroundSkin malformations that resembled manifestations of Ehlers-Danlos-Syndrome were described in a variety of domestic animals during the last century as cutis hyperelastica, hyperelastosis cutis, dermatosparaxis, dermal/collagen dysplasia, dermal/cutaneous asthenia or Ehlers-Danlos-like syndrome/s. In 2007, the mutation responsible for Hereditary Equine Regional Dermal Asthenia (HERDA) in Quarter Horses was discovered. Several case reports are available for similar malformations in other breeds than Qua… Show more
“…; Monthoux et al . ). A closely related phenotype is equine regional dermal asthenia (HERDA) in horses, which is caused by a variant in the PPIB gene (Tryon et al .…”
Ehlers-Danlos syndrome (EDS) is a group of heritable connective tissue disorders caused by defective collagen synthesis or incorrect assembly of the collagen triple helical structure. EDS is characterised by joint hypermobility, skin hyperextensibility, abnormal scarring, poor wound healing and tissue friability. Human EDS may be caused by variants in several different genes including COL5A1, which encodes the collagen type V alpha 1 chain. For the present study we investigated a 1.5-year-old, spayed female, domestic shorthair cat with EDS. The affected cat showed multiple recurrent skin tears, hyperextensibility of the skin and joint abnormalities. We obtained whole genome sequencing data from the affected cat and searched for variants in candidate genes known to cause EDS. We detected a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1: c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat.
“…; Monthoux et al . ). A closely related phenotype is equine regional dermal asthenia (HERDA) in horses, which is caused by a variant in the PPIB gene (Tryon et al .…”
Ehlers-Danlos syndrome (EDS) is a group of heritable connective tissue disorders caused by defective collagen synthesis or incorrect assembly of the collagen triple helical structure. EDS is characterised by joint hypermobility, skin hyperextensibility, abnormal scarring, poor wound healing and tissue friability. Human EDS may be caused by variants in several different genes including COL5A1, which encodes the collagen type V alpha 1 chain. For the present study we investigated a 1.5-year-old, spayed female, domestic shorthair cat with EDS. The affected cat showed multiple recurrent skin tears, hyperextensibility of the skin and joint abnormalities. We obtained whole genome sequencing data from the affected cat and searched for variants in candidate genes known to cause EDS. We detected a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1: c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat.
“…The mutation which causes Warmblood fragile foal syndrome (Monthoux et al . ), which is another form of EDS, has not been reported in Quarter Horses. Junctional epidermolysis bullosa (JEB) (Frame et al .…”
Section: Differential Diagnosesmentioning
confidence: 95%
“…Trauma in an unaffected horse could certainly cause wounds similar to those seen with HERDA; however, hyperextensible, loose skin and abnormal scarring are not generally present. The mutation which causes Warmblood fragile foal syndrome (Monthoux et al 2015), which is another form of EDS, has not been reported in Quarter Horses. Junctional epidermolysis bullosa (JEB) (Frame et al 1988;Kohn et al 1989;Lieto et al 2002) could be confused with HERDA but it only occurs in neonatal animals and has not previously been reported in Quarter Horses.…”
Summary
Hereditary equine regional dermal asthenia (HERDA) results from a genetic mutation which affects the skin and other tissues of Quarter Horses and horses with Quarter Horse lineage. The disease HERDA has an autosomal recessive mode of inheritance and has become a significant concern in the Quarter Horse industry due to the high frequency of heterozygote carriers. Affected homozygous horses appear normal at birth; however, within the first 2 years of life they usually acquire loose, hyperextensible skin and wounds which result in disfiguring scars either spontaneously or from minor trauma. Some severely affected horses also develop haematomas and seromas. Consequently, most affected horses are subjected to euthanasia at an early age. No treatment options other than palliative therapy currently exist. As part of a five panel test (http://www.aqha.com/News/News-Articles/2013/April/04292013-Genetic-Testing.aspx) the American Quarter Horse Association presently requires DNA testing for HERDA on all breeding stallions. There are currently no restrictions on registration of horses heterozygous or homozygous for the HERDA mutation. Due to the autosomal recessive nature of the disease, Quarter Horse mares and horses of all breeds from HERDA‐associated bloodlines should also be tested.
“…Hereditary Equine Regional Dermal Asthenia is caused by a missense mutation (c.115G>A) in the peptidylprolyl isomerase B (PPIB) gene [4]. Warmblood Fragile Foal Syndrome is also an autosomal recessive disease, but it affects Warmblood breeds [10][11][12][13][14]. The disease is caused by a missense mutation (c.2032G>A) in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene [5].…”
Section: Introductionmentioning
confidence: 99%
“…The disease is caused by a missense mutation (c.2032G>A) in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene [5]. Although the PLOD1 mutation has been identified in only one case report [14], there are four other case reports [10][11][12][13] published before the identification of the causative mutation where the animals were suspected to be affected by the same condition [14].…”
a b s t r a c tThe Ehlers-Danlos syndrome in horses is a group of genetic connective tissue disorders clinically characterized by skin fragility and hyperextensibility. To date, only two of those conditions (Hereditary Equine Regional Dermal Asthenia and Warmblood Fragile Foal Syndrome [WFFS]) have been characterized based on the causative genetic mutations. This report describes the dermatological and histological findings observed in a 3.5-year-old Mangalarga and Campolina crossbreed mare with recurrent skin wounds. Upon dermatological examination, the mare presented with hyperextensible, fragile, and thin skin areas, and scars distributed mainly along the dorsal regions. Histopathological evaluation of affected skin biopsies revealed collagen fibers abnormalities within the deep dermis. The complete PPIB coding region was amplified, but no mutations were observed. Moreover, the PLOD1 gene mutation responsible for WFFS was not present in this animal. To our knowledge, this is the first report describing a Brazilian non-Quarter horse mare with dermatological and histopathological findings of Ehlers-Danlos syndrome.
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