Warmblood fragile foal syndrome causative single nucleotide polymorphism frequency in horses in Ireland

Áine Rowe,Sharon Flanagan,Gerald Barry,Elizabeth A Lane,Lisa M Katz,Vivienne Duggan

doi:10.1186/s13620-021-00206-1

Abstract

BackgroundWarmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive disorder caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. Homozygosity for the mutation results in defective collagen synthesis which clinically manifests as the birth of non viable or still born foals with abnormally fragile skin. While the mutation has been identified in non Warmblood breeds including the Thoroughbred, to date all homozygous clinically affected cases reported in the scientific literature are Warmblood foals. The objective of this study was to investigate the carrier frequency of the mutation in the Thoroughbred and sport horse populations in Ireland.MethodsA test was developed at the UCD School of Veterinary Medicine using real-time PCR to amplify the PLOD1 gene c.2032G > A variant. A subset of the samples was also submitted to an external laboratory with a licensed commercial WFFS genetic test.ResultsWarmblood Fragile Foal Syndrome genotyping was performed on hair samples from 469 horses representing 6 different breeds. Six of 303 (1.98%) sport horses tested and three of 109 (2.75%) Thoroughbreds tested were heterozygous for the WFFS polymorphism (N/WFFS). The WFFS polymorphism was not identified in the Standardbred, Cob, Connemara, or other pony breeds.ConclusionsThe study identified a low frequency of the WFFS causative mutation in sport horses and Thoroughbreds in Ireland, highlighting the importance of WFFS genetic testing in order to identify phenotypically normal heterozygous carriers and to prevent the birth of nonviable foals.

Highlights

Warmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive disorder caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene
Two gene defects causing Ehlers Danlos like syndromes (EDLS) phenotypes in horses have been discovered, hereditary equine regional dermal asthenia (HERDA), a degenerative inherited autosomal recessive skin disorder occurring in Quarter Horses and related breeds [10], and Warmblood fragile foal syndrome (WFFS), a lethal congenital autosomal recessive disorder, which to date has only been reported in Warmblood foals [11, 12]; the
Three of 109 (2.75%) Thoroughbreds tested were heterozygous for the WFFS polymorphism (N/WFFS)

Summary

Introduction

Warmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive disorder caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. WFFS is caused by a point mutation (c.2032G > A, p.Gly678Arg) in the equine procollagen lysine, 2-oxoglutarate 5 -dioxygenase 1 (PLOD1) gene which encodes lysyl hydroxylase [12]. In humans, this enzyme catalyzes the hydroxylation of lysyl residues in collagen sequences, which serve as binding sites for galactose/glucosylgalactose units, allowing for intra and intermolecular crosslinking of collagen fibrils [17]. Deficiency of lysyl hydroxylase due to mutated PLOD1 in humans results in mechanical instability of affected connective tissue [18, 19]

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