Lyons Leslie A, Biller David S, Erdman Carolyn A, Lipinski Monika J, Young Amy E, Roe Bruce A, Qin Baifang, Grahn Robert A
Department of Population Health & Reproduction, School of Veterinary Medicine, One Shields Avenue, University of California, Davis, 95616, USA.
J Am Soc Nephrol. 2004 Oct;15(10):2548-55. doi: 10.1097/01.ASN.0000141776.38527.BB.
Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder in humans that causes the formation of fluid-filled renal cysts, often leading to renal failure. PKD1 mutations cause 85% of ADPKD. Feline PKD is autosomal dominant and has clinical presentations similar to humans. PKD affects approximately 38% of Persian cats worldwide, which is approximately 6% of cats, making it the most prominent inherited feline disease. Previous analyses have shown significant linkage between the PKD phenotype and microsatellite markers linked to the feline homolog for PKD1. In this report, the feline PKD1 gene was scanned for causative mutations and a C>A transversion was identified at c.10063 (human ref NM_000296) in exon 29, resulting in a stop mutation at position 3284, which suggests a loss of approximately 25% of the C-terminus of the protein. The same mutation has not been identified in humans, although similar regions of the protein are truncated. The C>A transversion has been identified in the heterozygous state in 48 affected cats examined, including 41 Persians, a Siamese, and several other breeds that have been known to outcross with Persians. In addition, the mutation is segregating concordantly in all available PKD families. No unaffected cats have been identified with the mutation. No homozygous cats have been identified, supporting the suggestion that the mutation is embryonic lethal. These data suggest that the stop mutation causes feline PKD, providing a test to identify cats that will develop PKD and demonstrating that the domestic cat is an ideal model for human PKD.
常染色体显性遗传性多囊肾病（ADPKD）是人类常见的遗传性疾病，会导致充满液体的肾囊肿形成，常引发肾衰竭。PKD1突变导致85%的ADPKD病例。猫的PKD是常染色体显性遗传，临床表现与人类相似。PKD影响全球约38%的波斯猫，约占猫总数的6%，使其成为最突出的遗传性猫病。先前的分析表明PKD表型与与猫PKD1同源的微卫星标记之间存在显著连锁。在本报告中，对猫的PKD1基因进行了致病突变扫描，在外显子29的c.10063（人类参考序列NM_000296）处鉴定到一个C>A颠换，导致第3284位出现终止突变，这表明该蛋白的C末端约25%缺失。虽然该蛋白的相似区域被截断，但在人类中尚未鉴定到相同的突变。在所检测的48只患病猫中，包括41只波斯猫、1只暹罗猫和其他几个已知与波斯猫杂交的品种，均鉴定到该C>A颠换处于杂合状态。此外，该突变在所有可用的PKD家系中均呈一致分离。未发现未受影响的猫携带该突变。未鉴定到纯合猫，这支持了该突变是胚胎致死的观点。这些数据表明该终止突变导致猫的PKD，为鉴定将患PKD的猫提供了检测方法，并证明家猫是人类PKD的理想模型。
