Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Vet Intern Med. 2012 Jul-Aug;26(4):935-44. doi: 10.1111/j.1939-1676.2012.00958.x.
Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs.
To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT).
Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1).
Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia.
A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37).
Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.
红细胞丙酮酸激酶（PK）缺乏症最初在巴森吉犬中被记录，是犬最常见的遗传性红细胞酶病。
报道 3 种新的特定品种 PK-LR 基因突变，并对小样本和选定的比格犬和西部高地白梗（WHWT）群体的 PK 突变进行回顾性调查。
拉布拉多猎犬（2 只同窝兄妹，5 只无关）、哈巴狗（2 只同窝兄妹，1 只无关）、比格犬（39 只贫血，29 只非贫血）、WHWT（22 只贫血，226 只非贫血）、凯恩梗（1 只）。
对年轻（<2 岁）、持续性高再生性溶血性贫血的犬的 PK-LR 基因外显子进行测序。
患有骨质疏松症、高血清铁蛋白浓度和严重肝继发性血色素沉着症的贫血拉布拉多猎犬同窝兄妹发现了 1 个无义突变（c.799C>T），导致提前出现终止密码子。贫血的哈巴狗和比格犬分别揭示了 2 种不同的错义突变（c.848T>C，c.994G>A），导致蛋白质结构和酶功能不可耐受的氨基酸变化。开发了特定品种的突变检测。在 248 只偏倚的 WHWT 中，9%和 35%分别为纯合子（受影响）和杂合子，携带先前描述的突变（突变等位基因频率为 0.26）。患有 PK 缺乏症的凯恩梗与受影响的 WHWT 具有相同的插入突变。在选择的 68 只比格犬中，35%为 PK 缺乏症，3%为携带者（0.37）。
红细胞 PK 缺乏症是由不同品种的不同突变引起的，由于慢性溶血和尚未解释的骨质疏松症，导致慢性严重溶血性贫血、血色素沉着症和继发性血色素沉着症。新开发的特定品种突变检测简化了 PK 缺乏症的诊断。
