Many lessons still to learn about autosomal dominant polycystic kidney disease.
Many lessons still to learn about autosomal dominant polycystic kidney disease.
复制标题
DOI：
10.1007/s44162-023-00017-8
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
我们仍在研究许多罕见疾病的遗传基础。在这里，我们提供了一个常染色体显性多囊肾病（ADPKD），最常见的遗传性肾脏疾病之一的患者的遗传景观分析的评论。包括表型优先和基因型优先的方法允许在该疾病人群中进行一些有趣且信息丰富的观察。PKD 1和PKD 2是ADPKD最常见的遗传原因，分别占7 - 8%和15%，而约7-8%的病例具有替代遗传诊断。这些罕见的形式包括IFT 140，GANAB，PKHD 1，HNF 1B，ALG 8和ALG 9。一些先前报道的可能致病的PKD 1和PKD 2等位基因可能具有降低的多态性，或者确实可能在其致病性方面被错误分类。关于所有形式的ADPKD的最新数据指出，在所有临床诊断为ADPKD的家庭以及具有更多非典型囊性肾表现的家庭中进行遗传学检查的重要性。在等位基因鉴定之后，尽可能进行分离分析仍然是至关重要的，以便我们继续了解肾衰竭的这些重要遗传原因。
We are still learning the genetic basis for many rare diseases. Here we provide a commentary on the analysis of the genetic landscape of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD), one of the most common genetic kidney diseases. Approaches including both phenotype first and genotype first allows some interesting and informative observations within this disease population. PKD1 and PKD2 are the most frequent genetic causes of ADPKD accounting for 78% and 15% respectively, whilst around 7–8% of cases have an alternative genetic diagnosis. These rarer forms include IFT140, GANAB, PKHD1, HNF1B, ALG8, and ALG9. Some previously reported likely pathogenic PKD1 and PKD2 alleles may have a reduced penetrance, or indeed may have been misclassified in terms of their pathogenicity. This recent data concerning all forms of ADPKD points to the importance of performing genetics tests in all families with a clinical diagnosis of ADPKD as well as those with more atypical cystic kidney appearances. Following allele identification, performing segregation analysis wherever possible remains vital so that we continue to learn about these important genetic causes of kidney failure.