A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.
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.
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Department of Surgical Research, Royal Alexandra Hospital for Children, Westmead, NSW 2145, Australia.
Croaker
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Zhang
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Manglick
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Cartmill
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Cass
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D000818:Animals; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D006627:Hirschsprung Disease / Q000235:genetics / Q000662:veterinary*; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009711:Nucleotides; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D009711:Nucleotides; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin