Open AccessGenetic cause for congenital methemoglobinemia in an Australian Pomeranian dog
Author(s) -
Zhou Shijia,
Tearle Rick,
Jozani Raziallah Jafari,
Winra Bethany,
Schaaf Olaf,
Nicholson Anthony,
Peaston Anne
Publication year - 2019
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.15435
Subject(s) - methemoglobinemia , missense mutation , medicine , mutation , genetics , mutant , stop codon , gene , biology , anesthesia
Little is known about genetic causes of congenital methemoglobinemia in dogs. Here, we report a CYB 5 R 3 mutation in a Pomeranian dog with congenital methemoglobinemia. A 6‐year‐old neutered female Pomeranian dog was investigated for cyanosis noticed during anesthesia for an orthopedic procedure. The history included lifelong mild exercise intolerance and bluish tongue. Methemoglobinemia was diagnosed using co‐oximetry. The CYB 5 R 3 gene was analyzed by comparing the patient's genomic DNA with the reference canine sequence. Mutation functional significance was investigated using snpEff and multispecies protein homology analyses. A homozygous missense single nucleotide CYB 5 R 3 mutation (ATC ➔ CTC at codon 194) caused a p.Ile194Leu substitution. The pIle194 residue is highly conserved in other mammals, supporting the likely pathogenicity of the substitution. The mutation described here is identical to that associated with familial methemoglobinemia in a family of Japanese Pomeranian dogs. This observation, together with the homozygous mutation found in our case, indicates that the mutant allele may be widespread within the Pomeranian breed internationally.