A Heterozygous Missense Variant in the COL5A2 in Holstein Cattle Resembling the Classical Ehlers–Danlos Syndrome

ClassicalEhlers-Danlossyndrome(cEDS)isaheritableconnectivetissuedisordercharacterizedbyvariabledegreesofskinhyperextensibilityandfragility,atrophicscarring,andgeneralizedjointhypermobility.ThepurposeofthisstudywastocharacterizetheclinicopathologicalphenotypeofacEDS‐affectedHolsteincalfandtoidentifythecausativegeneticvariantassociatedwiththedisorderbywhole‐genomesequencing(WGS).A3‐day‐oldfemaleHolsteincalfwasreferredbecauseofeasilyinducedskindetachmentandhyperextensibilityintheneck.Acompleteclinicalinvestigationwasperformedinthecalf,dam,andmaternal‐grandmother.Thecalfanddamshowedhyperextensibilityoftheneckskinandatrophicscarring;additionally,thecalfpresentedskinfragility.Moreover,thehistopathologyofbiopsiesfromthecalfanditsdamshowedthatthecollagenbundlesinaffectedskinareaswerewavy,short,thin,andsurroundedbyedemaandmoderatetosevereacutehemorrhages.GeneticanalysisrevealedaprivateheterozygousmissensevariantinCOL5A2(c.2366G>T;p.Gly789Val)thatwaspresentonlyinthecalfanddam.ThisconfirmedthediagnosisofcEDSandrepresentsthefirstreportofacausalvariantforcEDSincattleandthefirstCOL5A2‐relatedlargeanimalmodel.