Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses.
Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses.
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DOI：
10.3389/fped.2017.00221
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发表时间：
2017
影响因子：
2.6
通讯作者：
Bergmann C
中科院分区：
文献类型：
--
作者：
Bergmann C
常染色体隐性遗传性多囊肾病（ARPKD）是一种肝肾纤维囊性疾病，其特征是肾脏增大伴进行性肾功能丧失和胆管扩张以及先天性肝纤维化，导致部分患者门脉高压。PKHD 1基因突变是ARPKD的主要原因;然而，该疾病在遗传上并不像长期认为的那样同质，并且其他几种囊基因突变可以表型ARPKD。家族史通常是阴性的，无论是隐性的，但也往往是显性的疾病基因，由于新生突变或隐性遗传的变异基因，通常遵循显性模式，如主要ADPKD基因PKD 1和PKD 2。多囊肾是一种常见的肾病综合征，也是一种常见的肾病。减少疾病蛋白的剂量导致细胞稳态中涉及的关键机制的信号通路的破坏，这可能有助于解释一些PKD患者的疾病进程的加速和严重的临床进展。全面了解致病基因对于咨询和避免遗传误诊是必不可少的，这在产前环境中尤其重要（例如，胚胎植入前遗传学诊断（Preimplantation Genetic Diagnosis/PGD）。对于ARPKD，有强烈的需求，早期和可靠的产前诊断，这是唯一可行的分子遗传学分析。明确的基因诊断有助于许多家庭，并改善患者的临床管理。可以避免不必要的和侵入性的措施，并在临床过程中早期发现肾和肾外共病。越来越多的基因必须考虑受益于下一代测序（NGS）的进步，它允许在一个单一的测试中以相对低的成本同时分析一大组基因，并已成为基因诊断的支柱。囊性和多囊肾疾病广泛的表型和遗传异质性使NGS成为治疗这些适应症的特别有效的方法。遗传数据的解释成为挑战，需要深入的临床理解。
Autosomal recessive polycystic kidney disease (ARPKD) is a hepatorenal fibrocystic disorder that is characterized by enlarged kidneys with progressive loss of renal function and biliary duct dilatation and congenital hepatic fibrosis that leads to portal hypertension in some patients. Mutations in the PKHD1 gene are the primary cause of ARPKD; however, the disease is genetically not as homogeneous as long thought and mutations in several other cystogenes can phenocopy ARPKD. The family history usually is negative, both for recessive, but also often for dominant disease genes due to de novo arisen mutations or recessive inheritance of variants in genes that usually follow dominant patterns such as the main ADPKD genes PKD1 and PKD2. Considerable progress has been made in the understanding of polycystic kidney disease (PKD). A reduced dosage of disease proteins leads to the disruption of signaling pathways underlying key mechanisms involved in cellular homeostasis, which may help to explain the accelerated and severe clinical progression of disease course in some PKD patients. A comprehensive knowledge of disease-causing genes is essential for counseling and to avoid genetic misdiagnosis, which is particularly important in the prenatal setting (e.g., preimplantation genetic diagnosis/PGD). For ARPKD, there is a strong demand for early and reliable prenatal diagnosis, which is only feasible by molecular genetic analysis. A clear genetic diagnosis is helpful for many families and improves the clinical management of patients. Unnecessary and invasive measures can be avoided and renal and extrarenal comorbidities early be detected in the clinical course. The increasing number of genes that have to be considered benefit from the advances of next-generation sequencing (NGS) which allows simultaneous analysis of a large group of genes in a single test at relatively low cost and has become the mainstay for genetic diagnosis. The broad phenotypic and genetic heterogeneity of cystic and polycystic kidney diseases make NGS a particularly powerful approach for these indications. Interpretation of genetic data becomes the challenge and requires deep clinical understanding.
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影响因子：
4
作者：
Bergmann, C;Küpper, F;Zerres, K
通讯作者：
Zerres, K
影响因子：
4.7
作者：
Boddu, Ravindra;Yang, Chaozhe;O'Connor, Amber K.;Hendrickson, Robert Curtis;Boone, Braden;Cui, Xiangqin;Garcia-Gonzalez, Miguel;Igarashi, Peter;Onuchic, Luiz F.;Germino, Gregory G.;Guay-Woodford, Lisa M.
通讯作者：
Guay-Woodford, Lisa M.
影响因子：
3.9
作者：
Bergmann, C;Senderek, J;Zerres, K
通讯作者：
Zerres, K
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Bergmann, Carsten;Fliegauf, Manfred;Omran, Heymut
通讯作者：
Omran, Heymut