OMIA 000327-9796 : Ehlers-Danlos syndrome in Equus caballus

In other species: dog , domestic cat , sheep , rabbit , American mink

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 120150 , 130000 , 130010 , 130020 , 130050 , 130060 , 130070 , 130080 , 130090 , 147900 , 225310 , 225320 , 225400 , 225410 , 229200 , 305200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: Also known as cutaneous asthenia (CA) or hyperelastosis cutis (HC). Some animals are born with easily extendible and very fragile skin. Severe lacerations result from the slightest scratch. The basic cause of these severe clinical signs is the presence of abnormal collagen in the skin. There are several genes encoding peptides that form procollagen molecules. There are also several genes encoding enzymes that remove excess amino acids from each end of the procollagen molecules, creating mature collagen. Mutations in any of these genes can give rise to Ehlers-Danlos syndrome. In general, mutations in collagen structural genes result in dominant forms of the disorder, because heterozygotes produce 50 per cent abnormal collagen molecules. In contrast, mutations in the genes for the enzymes that "process" procollagen generally result in recessive forms of the disorder, because the 50 per cent of normal enzyme activity that occurs in heterozygotes is sufficient to "process" all procollagen molecules. In humans, a detailed classification of the different types of Ehlers-Danlos syndrome has been made, corresponding to mutations in the different genes involved. In animals, most occurrences of the disorder have to be lumped together because the detailed studies necessary for classification have not yet been conducted.

Species-specific name: Hereditary equine regional dermal asthenia; hyperelastosis cutis

Species-specific symbol: HERDA

History: As noted by Tyron et al. (2007), their study was "the first whole-genome scan used to identify a novel disease gene in the horse".

Inheritance: Tryon et al. (2005) provided convincing evidence of autosomal recessive inheritance in Quarter horses.

Mapping: By conducting a genome scan on 38 affected and 44 unrelated normal horses, each genotyped with 98 autosomal microsatellites, Tryon et al. (2007) used homozygosity mapping to map this disorder to a 20cM region on chromosome ECA1. Fine-mapping narrowed this region to a 2.5Mb, which (based on deductions from comparative mapping) contains around 20 genes.

Molecular basis: By sequencing the most likely of the roughly 20 positional candidate genes (see Mapping section), Tyron et al. (2007) identified a likely causative missense mutation (c.115G>A; p.39G>R) in the gene for cyclophilin B (PPIB).

Ishikawa et al. (2012) confirmed the above mutation as causal, but identified it as c.115G>A; p.6G>R rather than c.115G>A; p.39G>R.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PPIB peptidylprolyl isomerase B (cyclophilin B) Equus caballus 1 NC_009144.3 (129306966..129312884) PPIB Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
American Quarter Horse Ehlers-Danlos syndrome PPIB missense EquCab2 1 g.128056148G>A c.115G>A p.G39R 2007 17498917 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Li 李靖, J., Liu, B., Yu, F., Liu, T., Peng, Y., Fu, Y. :
A 2-Year-Old Filly With Hereditary Equine Regional Dermal Asthenia: The First Case Report From China. J Equine Vet Sci 64:1-4, 2018. Pubmed reference: 30973143. DOI: 10.1016/j.jevs.2018.01.010.
2017 Brinkman, E.L., Weed, B.C., Patnaik, S.S., Brazile, B.L., Centini, R.M., Wills, R.W., Olivier, B., Sledge, D.G., Cooley, J., Liao, J., Rashmir-Raven, A.M. :
Cardiac findings in Quarter Horses with heritable equine regional dermal asthenia. J Am Vet Med Assoc 250:538-547, 2017. Pubmed reference: 28207320. DOI: 10.2460/javma.250.5.538.
2014 Badial, P.R., Oliveira-Filho, J.P., Winand, N.J., Borges, A.S. :
Allele frequency of hereditary equine regional dermal asthenia in American Quarter horses in Brazil determined by quantitative real-time PCR with high resolution melting analysis. Vet J 199:306-7, 2014. Pubmed reference: 24355815. DOI: 10.1016/j.tvjl.2013.11.008.
Bowser, J.E., Elder, S.H., Pasquali, M., Grady, J.G., Rashmir-Raven, A.M., Wills, R., Swiderski, C.E. :
Tensile properties in collagen-rich tissues of Quarter Horses with hereditary equine regional dermal asthenia (HERDA). Equine Vet J 46:216-22, 2014. Pubmed reference: 23738970. DOI: 10.1111/evj.12110.
Halper, J. :
Connective tissue disorders in domestic animals. Adv Exp Med Biol 802:231-40, 2014. Pubmed reference: 24443030. DOI: 10.1007/978-94-007-7893-1_14.
2013 Rashmir-Raven, A. :
Heritable equine regional dermal asthenia. Vet Clin North Am Equine Pract 29:689-702, 2013. Pubmed reference: 24267684. DOI: 10.1016/j.cveq.2013.09.001.
Steelman, S.M.J.N.D., Conant, E., Juras, R., Cothran, E.G., Edwards, J.F., Chowdhary, B.P. :
Ehlers-Danlos syndrome in a Quarter Horse gelding: a case report of PPIB-independent HERDA. Journal of Equine Veterinary Science 34:565-568, 2013.
2012 Boudko, S.P., Ishikawa, Y., Lerch, T.F., Nix, J., Chapman, M.S., Bächinger, H.P. :
Crystal structures of wild-type and mutated cyclophilin B that causes hyperelastosis cutis in the American quarter horse. BMC Res Notes 5:626, 2012. Pubmed reference: 23137129. DOI: 10.1186/1756-0500-5-626.
Ishikawa, Y., Vranka, J.A., Boudko, S.P., Pokidysheva, E., Mizuno, K., Zientek, K., Keene, D.R., Rashmir-Raven, A.M., Nagata, K., Winand, N.J., Bächinger, H.P. :
Mutation in cyclophilin B that causes hyperelastosis cutis in American Quarter Horse does not affect peptidylprolyl cis-trans isomerase activity but shows altered cyclophilin B-protein interactions and affects collagen folding. J Biol Chem 287:22253-65, 2012. Pubmed reference: 22556420. DOI: 10.1074/jbc.M111.333336.
2011 Marshall, V.L., Secombe, C., Nicholls, P.K. :
Cutaneous asthenia in a Warmblood foal. Aust Vet J 89:77-81, 2011. Pubmed reference: 21323653. DOI: 10.1111/j.1751-0813.2010.00683.x.
White, S.D., Bourdeau, P. :
Prevalence of the mutation in cyclophilin B (PPIB), a causal candidate gene for HERDA, among Quarter Horses in France. Vet Dermatol 22:206-8, 2011. Pubmed reference: 21118319. DOI: 10.1111/j.1365-3164.2010.00941.x.
2010 Mochal, C.A., Miller, W.W., Cooley, A.J., Linford, R.L., Ryan, P.L., Rashmir-Raven, A.M. :
Ocular findings in Quarter Horses with hereditary equine regional dermal asthenia. J Am Vet Med Assoc 237:304-10, 2010. Pubmed reference: 20673112. DOI: 10.2460/javma.237.3.304.
2009 Grady, J.G., Elder, S.H., Ryan, P.L., Swiderski, C.E., Rashmir-Raven, A.M. :
Biomechanical and molecular characteristics of hereditary equine regional dermal asthenia in Quarter Horses. Vet Dermatol 20:591-9, 2009. Pubmed reference: 20178499. DOI: 10.1111/j.1365-3164.2009.00830.x.
Tryon, RC., Penedo, MC., McCue, ME., Valberg, SJ., Mickelson, JR., Famula, TR., Wagner, ML., Jackson, M., Hamilton, MJ., Nooteboom, S., Bannasch, DL. :
Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. J Am Vet Med Assoc 234:120-5, 2009. Pubmed reference: 19119976. DOI: 10.2460/javma.234.1.120.
2007 Tryon, RC., White, SD., Bannasch, DL. :
Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse. Genomics 90:93-102, 2007. Pubmed reference: 17498917. DOI: 10.1016/j.ygeno.2007.03.009.
2005 Borges, A.S., Conceição, L.G., Alves, A.L., Fabris, V.E., Pessoa, M.A. :
Hereditary equine regional dermal asthenia in three related Quarter horses in Brazil. Vet Dermatol 16:125-30, 2005. Pubmed reference: 15842544. DOI: 10.1111/j.1365-3164.2005.00431.x.
Tryon, RC., White, SD., Famula, TR., Schultheiss, PC., Hamar, DW., Bannasch, DL. :
Inheritance of hereditary equine regional dermal asthenia in Quarter Horses. Am J Vet Res 66:437-42, 2005. Pubmed reference: 15822588.
2004 White, S.D., Affolter, V.K., Bannasch, D.L., Schultheiss, P.C., Hamar, D.W., Chapman, P.L., Naydan, D., Spier, S.J., Rosychuk, R.A., Rees, C., Veneklasen, G.O., Martin, A., Bevier, D., Jackson, H.A., Bettenay, S., Matousek, J., Campbell, K.L., Ihrke, P.J. :
Hereditary equine regional dermal asthenia ("hyperelastosis cutis") in 50 horses: clinical, histological, immunohistological and ultrastructural findings. Vet Dermatol 15:207-17, 2004. Pubmed reference: 15305927. DOI: 10.1111/j.1365-3164.2004.00402.x.
1999 Esser, M., Niederacher, V., Pfeffer, K., Scheuer, H. :
über die selten auftretende Dermatosparaxie (Ehlers-Danlos-Syndrom) bei einem Fohlen - ein Fallbericht. [Dermatosparaxis (Ehlers-Danlos-Syndrome) in a newborn foal - a case report] Pferdeheilkunde 15:434-436, 1999.
1988 Hardy, M.H., Fisher, K.R.S., Vrablic, O.E., Yager, J.A., Nimmo-Wilkie, J.S., Parker, W., Keeley, F.W. :
An inherited connective tissue disease in the horse Laboratory Investigation 59:253-262, 1988. Pubmed reference: 3404977.
1984 Solomons, B. :
Equine cutis hyperelastica. Equine Vet J 16:541-2, 1984. Pubmed reference: 6519046.
Witzig, P., Suter, M., Wild, P., Rao, V.H., Steinmann, B., von Rotz, A. :
[Dermatosparaxis in a foal and a cow--a rare disease?]. Schweiz Arch Tierheilkd 126:589-96, 1984. Pubmed reference: 6515392.

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  • Created by Frank Nicholas on 04 Sep 2007
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