PDF(Pubmed)
Abstract：
Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability in phenotype and risk of subsequent kidney failure. Despite an established genotype-phenotype correlation in cystic kidney diseases, incomplete penetrance and variable disease expressivity are present as is the case in all monogenic diseases. In family members with autosomal dominant polycystic kidney disease (ADPKD), the same causal variant is responsible in all affected family members; however, there can still be striking discordance in phenotype severity. This narrative review explores contributors to within-family discordance in ADPKD severity. Cases of biallelic and digenic inheritance, where 2 rare pathogenic variants in cystogenic genes are coexistent in one family, account for a small proportion of within-family discordance. Genetic background, including cis and trans factors and the polygenic propensity for comorbid disease, also plays a role but has not yet been exhaustively quantified. Environmental exposures, including diet; smoking; alcohol, salt, and protein intake, and comorbid diseases, including obesity, diabetes, hypertension, kidney stones, dyslipidemia, and additional coexistent kidney diseases all contribute to ADPKD phenotypic variability among family members. Given that many of the factors contributing to phenotype variability are preventable, modifiable, or treatable, health care providers and patients need to be aware of these factors and address them in the treatment of ADPKD.
摘要：
超过100个基因中的数千个致病变异可导致肾囊肿，其表型和随后的肾衰竭风险具有显著的变异性。尽管在囊性肾病中已确定基因型-表型相关性，在所有单基因疾病中都存在不完全的外显率和可变的疾病表达率。在常染色体显性遗传性多囊肾病（ADPKD）的家族成员中，相同的因果变异对所有受影响的家庭成员负责；然而，表型严重程度仍可能存在显著的不一致。这篇叙述性综述探讨了家庭内部ADPKD严重程度不一致的原因。双等位基因和双基因遗传的病例，其中2个罕见的致病变种在一个家族中共存，占家庭内部不和谐的一小部分。遗传背景,包括顺式和反式因素以及共病的多基因倾向，也起作用，但尚未详尽量化。环境暴露,包括饮食；吸烟；酒精，盐,和蛋白质的摄入，和合并症，包括肥胖,糖尿病,高血压,肾结石,血脂异常,和其他共存的肾脏疾病都有助于家庭成员之间的ADPKD表型变异。鉴于导致表型变异性的许多因素是可以预防的，可修改，或可治疗，卫生保健提供者和患者需要意识到这些因素,并在ADPKD的治疗中解决这些因素.
