PDF(Pubmed)
Abstract：
A precise diagnosis in medicine allows appropriate disease-specific management. Kidney failure of unknown aetiology remains a frequent diagnostic label within the haemodialysis unit and kidney transplant clinic, accounting for 15-20% of these patients. Approximately 10% of such cases may have an underlying monogenic cause of kidney failure. Modern genetic approaches can provide a precise diagnosis for patients and their families. A search for extra-renal disease manifestations is also important as this may point to a specific genetic diagnosis. Here, we present two patients where molecular genetic testing was performed because of kidney failure of unknown aetiology and associated retinal phenotypes. The first patient reached kidney failure at 16 years of age but only presented with a retinal phenotype at 59 years of age and was found to have evidence of rod-cone dystrophy. The second patient presented with childhood kidney failure at the age of 15 years and developed visual difficulties and photophobia at the age of 32 years and was diagnosed with cone dystrophy. In both cases, genetic tests were performed which revealed a homozygous whole-gene deletion of NPHP1-encoding nephrocystin-1, providing the unifying diagnosis of Senior-Løken syndrome type 1. We conclude that reviewing kidney and extra-renal phenotypes together with targeted genetic testing was informative in these cases of kidney failure of unknown aetiology and associated retinal phenotypes. The involvement of an interdisciplinary team is advisable when managing such patients and allows referral to other relevant specialities. The long time lag and lack of diagnostic clarity and clinical evaluation in our cases should encourage genetic investigations for every young patient with unexplained kidney failure. For these and similar patients, a more timely genetic diagnosis would allow for improved management, a risk assessment of kidney disease in relatives, and the earlier identification of extra-renal disease manifestations.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s44162-024-00031-4.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s44162-024-00031-4.
摘要：
医学上的精确诊断允许适当的疾病特异性管理。病因不明的肾功能衰竭仍然是血液透析单位和肾脏移植诊所的常见诊断标签。占这些患者的15-20%。大约10%的此类病例可能具有肾衰竭的潜在单基因原因。现代遗传学方法可以为患者及其家人提供精确的诊断。寻找肾外疾病表现也很重要，因为这可能指向特定的遗传诊断。这里,我们介绍了2例因病因不明和相关视网膜表型的肾衰竭而进行分子遗传学检测的患者.第一位患者在16岁时达到肾衰竭，但仅在59岁时出现视网膜表型，并发现有杆锥营养不良的证据。第二名患者在15岁时出现儿童肾衰竭，在32岁时出现视力困难和畏光，并被诊断为锥体营养不良。在这两种情况下，进行了遗传测试，发现编码NPHP1的肾囊肿蛋白1的纯合全基因缺失，为高级Løken综合征1型提供了统一的诊断。我们得出的结论是，在这些病因不明和相关视网膜表型的肾衰竭病例中，回顾肾脏和肾外表型以及靶向基因检测可提供信息。在管理此类患者时，建议跨学科团队的参与，并允许转诊其他相关专业。在我们的病例中，长期滞后且缺乏诊断清晰度和临床评估，应鼓励对每位无法解释的肾衰竭的年轻患者进行遗传调查。对于这些和类似的患者，更及时的基因诊断可以改善管理，亲属肾脏疾病的风险评估，以及早期发现肾外疾病的表现。
■在线版本包含10.1007/s44162-024-00031-4提供的补充材料。
■在线版本包含10.1007/s44162-024-00031-4提供的补充材料。
