A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.
Abstract: Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification-created restriction site (ACRS) technique, revealed a dinucleotide TC-->AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.
Publication Date: 1998-06-13 PubMed ID: 9580670DOI: 10.1093/hmg/7.6.1047Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Arabian Horses
- Case Reports
- Clinical Examination
- Clinical Findings
- Clinical Pathology
- Congenital Disorders
- Diagnosis
- Disease Diagnosis
- Equine Diseases
- Equine Health
- Genetics
- Horses
- Immune Response
- Immune System
- Inflammation
- Leukocytes
- Neutrophils
- Veterinary Care
- Veterinary Medicine
- Veterinary Practice
- Veterinary Research
- White Blood Cells
Summary
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The study records a first-ever documented case of a horse born with Pelger-Huët anomaly (PHA), a rare genetic disorder that affects the neutrophils, the most common type of white blood cells. The horse, a 1.5-year-old Arabian male, showed symptoms consistent with PHA and similar findings were observed in the horse’s sire and his siblings.
Background
- The research revolves around a 1.5-year-old Arabian horse presented to the Louisiana State University Veterinary Teaching Hospital and Clinic with a deep trunk laceration. The condition triggered an initial investigation into the horse’s blood cell characteristics.
Initial Observations and Diagnosis
- Early complete blood count (CBC) results exhibited an inflammatory leukogram, indicating an ongoing inflammatory or infection process. This was characterized by a significant degenerative left shift, i.e., an abnormal increase in immature band neutrophils. No mature, segmented neutrophils were detected.
- Abdominal ultrasonography revealed the presence of excess fluid in the abdominal cavity, which consisted of a large quantity of neutrophils. These neutrophils displayed hyposegmentation, i.e., they had fewer segments than normal, and condensed mature chromatin structure.
- Neutrophil morphology on the initial blood smear matched with that observed in cells in the abdominal fluid, affirming the diagnosis of Pelger-Huët anomaly (PHA) in the young horse.
Confirmation of Congenital PHA
- The PHA condition was confirmed to be congenital, or hereditary, based on a series of blood smears showing persistent neutrophil hyposegmentation.
- Ruling out acquired causes of PHA was crucial to consolidating this diagnosis. Acquired PHA is usually associated with malignancies, or can be drug-induced. As no such factors were involved, the anomaly was deemed inborn.
- A supporting factor for the diagnosis was similar neutrophil hyposegmentation noticed on blood smears obtained from the colt’s biological father and his siblings.
Significance and Conclusion
- The documented case is the first known instance of congenital PHA in a horse. This notable finding impacts veterinary clinical pathology and genetics studies as it paves the way to furthering the examination of inherited white blood cell anomalies in animals.
Cite This Article
APA
Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D.
(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.
https://doi.org/10.1093/hmg/7.6.1047 Publication
Researcher Affiliations
- Department of Surgical Research, Royal Alexandra Hospital for Children, Westmead, NSW 2145, Australia.
MeSH Terms
- Animals
- DNA Mutational Analysis
- DNA, Complementary
- Hirschsprung Disease / genetics
- Hirschsprung Disease / veterinary
- Horse Diseases / genetics
- Horses
- Humans
- Molecular Sequence Data
- Mutation
- Nucleotides
- Receptor, Endothelin B
- Receptors, Endothelin / genetics
- Sequence Homology, Amino Acid
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