Nephron. 2019;141(1):50-60. doi: 10.1159/000493532. Epub 2018 Oct 25.
Early and severe forms of polycystic kidney disease (PKD) do already manifest during childhood or adolescence. They are characterized by enlarged kidneys and diminished renal function that prenatally may result in Potter's oligohydramnios sequence. Genetically, various defects can mimic this phenotype. Most common are PKHD1 mutations that lead to autosomal recessive PKD (ARPKD). About the same number of children do carry mutations in the dominant autosomal dominant polycystic kidney disease (ADPKD) genes, PKD1 and less frequent PKD2, often arise de novo or may affect both disease alleles in a recessive mode. Mutations in DZIP1L have been recently described to result in an ARPKD-like phenotype. Likewise, mutations in several other cystogenes can phenocopy early and severe PKD. Early and reliable prenatal diagnosis for which there is a strong demand in ARPKD and related diseases is feasible only by genetics. A comprehensive knowledge of disease-causing genes is essential for the correct diagnosis and parental counselling. The increasing number of genes that need to be considered benefits from the advances of next generation sequencing and allows the simultaneous analysis of all genes of interest in a single test, which is now the mainstay for genetic diagnosis. Interpretation of data is challenging and requires expert knowledge in data handling, bioinformatics and clinical genetics.
早发型和严重型多囊肾病 (PKD) 在儿童期或青春期即可显现。其特征为肾脏增大和肾功能下降，在产前可能导致波特氏序列的羊水过少。在遗传上，各种缺陷可模拟这种表型。最常见的是导致常染色体隐性多囊肾病 (ARPKD) 的 PKHD1 突变。约相同数量的儿童携带常染色体显性多囊肾病 (ADPKD) 基因，PKD1 和较不常见的 PKD2 的突变，这些突变通常为新生突变，或可能以隐性模式影响两个疾病等位基因。最近已描述 DZIP1L 突变可导致 ARPKD 样表型。同样，几个其他囊性基因的突变也可模拟早发型和严重型 PKD。ARPKD 和相关疾病的强烈需求使得早发型和可靠的产前诊断成为可能，但仅通过遗传学实现。全面了解致病基因对于正确的诊断和父母咨询至关重要。需要考虑的基因数量不断增加，得益于下一代测序的进步，并允许在单次测试中同时分析所有感兴趣的基因，这是目前遗传诊断的基础。数据解释具有挑战性，需要在数据处理、生物信息学和临床遗传学方面具有专业知识。
