Overo lethal white foal syndrome, OLWFS

(Megacolon, Hirschsprung disease)

 

Gene: EDNRB

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, EDNRB gene; c.353-4, TC>AG, p.(I118K), exon1

Medical system: Neurological, digestive

Breed: Paint Horse, « Overo »

Age of onset of symptoms: At birth

The EDNRB gene influences the migration of melanocytes during development, to give a white (overo) spotted coat when one copy is mutated.  When both copies of the gene are mutated, there is an almost complete inhibition of the migration of melanocytes to give a white foal.  However, a double mutation also inhibits the cells which innervate the intestines causing a paralysis of the large intestine.  The result is an intestinal blockage, accumulation of feces and dilation of the large intestine, a condition called “megacolon”.  At birth, the foal affected by “White Foal Syndrome” is completely white, with blue eyes and pink skin. The foal’s behavior is initially normal although it is not able to expel its meconium. Signs of colic appear between 12 and 16 hours after birth.  These signs worsen and the animal does not respond to medical treatment. The affected foal dies within 48 hours if it is not euthanized beforehand.

 

References:

OMIA link: [0629-9796]

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Badial PR, Teixeira RBC, Delfiol DJZ, et al. (2018) Validation of High-Resolution Melting Analysis as a Diagnostic Tool for Endothelin Receptor B Mutation in American Paint Horses and Allele Frequency Estimation. Mol Cell Probes. 41:52-56 [pubmed/30096357]

Ayala-Valdovinos MA, Galindo-García J, Sánchez-Chiprés D, Duifhuis-Rivera T. (2016) New Test for Endothelin Receptor Type B (EDNRB) Mutation Genotyping in Horses Mol Cell Probes. 30(3):182-4. [pubmed/27039359]

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Tryon RC, Penedo MC, McCue ME, et al. (2009) Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. J Am Vet Med Assoc. 234(1):120-5. [pubmed/19119976]

Santschi EM, Vrotsos PD, Purdy AK, et al. (2001) Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses. Am J Vet Res. 62(1):97-103. [pubmed/11197568]

Metallinos DL, Bowling At, Rine J. (1998) A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease.  Mamm Genome 9(6):426-431.  [pubmed/9585428]

Santschi EM, Purdy AK, Valberg SJ, et al. (1998) Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses. Mamm Genome. 9(4):306-309. [pubmed/9530628]

Yang GC, Croaker D, Zhang AL, et al. (1998) A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.  Hum Mol Genet 7(6):1047-1052. [pubmed/9580670]