Zhou Shijia, Tearle Rick, Jozani Raziallah Jafari, Winra Bethany, Schaaf Olaf, Nicholson Anthony, Peaston Anne
School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia.
J Vet Intern Med. 2019 Mar;33(2):868-873. doi: 10.1111/jvim.15435. Epub 2019 Feb 14.
Little is known about genetic causes of congenital methemoglobinemia in dogs. Here, we report a CYB R 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 R 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 R 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.
关于犬先天性高铁血红蛋白血症的遗传病因，人们了解甚少。在此，我们报告一只患有先天性高铁血红蛋白血症的博美犬存在CYBR突变。一只6岁已绝育的雌性博美犬因在骨科手术麻醉期间出现发绀而接受检查。病史包括终生轻度运动不耐受和舌头发蓝。通过共血氧测定法诊断为高铁血红蛋白血症。通过将患者的基因组DNA与参考犬序列进行比较来分析CYBR基因。使用snpEff和多物种蛋白质同源性分析来研究突变的功能意义。一个纯合错义单核苷酸CYBR突变（密码子194处的ATC→CTC）导致了p.Ile194Leu替换。pIle194残基在其他哺乳动物中高度保守，支持了该替换可能具有致病性。此处描述的突变与日本博美犬家族中的家族性高铁血红蛋白血症相关的突变相同。这一观察结果，连同我们病例中发现的纯合突变，表明该突变等位基因可能在国际博美犬品种中广泛存在。
