■常染色体显性多囊肾病(ADPKD)是一种常见的遗传性疾病。PKD1基因负责大多数ADPKD病例,该基因的突变表现出高度的遗传多样性。本研究旨在通过家系分析研究PKD1基因突变的ADPKD患者基因型与表型之间的关系。
■使用外周血DNA的全外显子组测序(WES)分析了八个受ADPKD影响的中国家系。使用Sanger测序验证鉴定的变体,收集和分析患者及其家属的临床资料。
■在所有家系中发现了PKD1中的9个新突变位点,包括c.4247T>G,c.3298_3301delGAGT,c.4798A>G,c.7567G>A,c.11717G>C,c.7703+5G>C,c.3296G>A,c.8515_8516insG,和c.5524C>A.发现这些突变与一系列临床表型有关,包括慢性肾病,高血压,多囊肝.发病年龄和疾病进展在家系间表现出显著的异质性,一些个体表现出早期发病和快速疾病进展,而其他人则无症状或有较轻的疾病症状。遗传模式支持常染色体显性遗传,因为受影响的个体继承了受影响的父母的突变。然而,有携带突变的个体仍然无症状或表现出更温和的疾病表型。
■本研究强调了全面基因型分析在了解ADPKD的进展和预后方面的重要性。新突变位点的鉴定扩展了我们对PKD1基因突变的认识。这些发现有助于更好地理解疾病,并可能对个性化治疗策略有影响。
UNASSIGNED: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis.
UNASSIGNED: Eight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed.
UNASSIGNED: Nine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes.
UNASSIGNED: This study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.