Reeders S T, Breuning M H, Davies K E, Nicholls R D, Jarman A P, Higgs D R, Pearson P L, Weatherall D J
Nature. 1985;317(6037):542-4. doi: 10.1038/317542a0.
Adult polycystic kidney disease (APCKD) is a common and often lethal multi-organ disease with an autosomal dominant pattern of inheritance; approximately 1 in 1,000 people carry the mutant gene. The major pathological abnormality is the development and progressive enlargement of cysts in several organs including the liver, pancreas and spleen as well as the kidneys. The basic biochemical defect which leads to the formation of cysts remains unknown. Cyst development, which is not retarded by any known therapy, leads to irreversible renal failure and death at a mean age of 51 unless dialysis or transplantation are used. Patients with the disease account for 9% of chronic dialysis requirement. The first symptoms tend to occur in the fourth decade, after most patients have reproduced. Presymptomatic diagnosis depends on the ultrasonographic detection of cysts, but exclusion cannot be achieved by this means; 34% of at-risk patients in the second decade and 14% in the third will go on to develop cysts after negative diagnosis. The low sensitivity of diagnostic techniques in this critical age-range imposes severe limitations on genetic counselling and the condition cannot be identified prenatally. Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05).
成人多囊肾病（APCKD）是一种常见且往往致命的多器官疾病，呈常染色体显性遗传模式；约每1000人中就有1人携带突变基因。主要病理异常是包括肝脏、胰腺、脾脏以及肾脏在内的多个器官中囊肿的形成和逐渐增大。导致囊肿形成的基本生化缺陷尚不清楚。囊肿的发展不受任何已知治疗方法的抑制，会导致不可逆转的肾衰竭，平均51岁时死亡，除非进行透析或移植。该病患者占慢性透析需求的9%。最初症状往往在大多数患者生育后的第四个十年出现。症状前诊断依赖于超声检测囊肿，但无法通过这种方式排除；在第二个十年中，34%的高危患者和第三个十年中14%的高危患者在诊断为阴性后仍会继续发展为囊肿。在这个关键年龄范围内诊断技术的低敏感性对遗传咨询造成了严重限制，且无法在产前识别该疾病。因此，我们寻找了成人多囊肾病的连锁标记；我们在此表明，成人多囊肾病基因座与16号染色体短臂上的α-珠蛋白基因座紧密连锁（Z值 = 25.85，θ值 = 0.05）。
