Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease
Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease
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DOI：
10.1007/s12072-021-10176-9
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发表时间：
2021-04-02
影响因子：
6.6
通讯作者：
Mochizuki, Toshio
中科院分区：
文献类型：
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作者：
Kataoka, Hiroshi;Watanabe, Saki;Mochizuki, Toshio
背景：大多数常染色体显性多囊肾病（ADPKD）患者随着年龄的增长会出现肝囊肿和多囊肝病。到目前为止，还没有一个简单的临床指标被证实可以预测多囊性肝病的恶化。此外，突变的类型和位置对多囊性肝病疾病进展的影响尚不清楚。在这里，我们旨在建立一个简单的肝囊肿指标，用于临床实践，并研究基因突变是否决定了常染色体显性多囊肾病患者的肝脏表型。方法共纳入129例ADPKD患者，根据突变类型（截断突变：无义突变、移码突变、剪接突变；非截断突变：替代突变）和突变位置评估肝囊肿指标。根据肝囊肿的数量、最大直径和与肝脏的面积比，采用Gigot和Drenth分类来确定肝囊肿的严重程度。结果多囊性肝病的总患病率为62.8%。PKD1无义突变（PKD1截断突变的一种）患者比没有突变的患者表现出更严重的肝脏疾病表型。我们确定最大直径为潜在的肝囊肿指标。此外，包括PKD1无义突变队列在内的亚组分析显示，位于PKD1 5MODIFIER LETTER PRIME末端的基因突变与最大直径指数值>= 6 cm相关。结论PKD1无链突变与肝囊肿严重程度相关，与最大直径指数共同作为肝囊肿的简单临床指标，可改善ADPKD多囊性肝病的治疗。
Background Most patients with autosomal-dominant polycystic kidney disease (ADPKD) develop liver cysts and polycystic liver disease as they age. To date, no simple clinical indicator has been confirmed to predict polycystic liver disease exacerbation. Furthermore, the effect of the type and location of mutation on disease progression of polycystic liver disease remains unclear. Here, we aimed to establish a simple liver cyst indicator for clinical practice and investigate whether gene mutations determined liver phenotype in patients with autosomal-dominant polycystic kidney disease. Methods In total, 129 patients with ADPKD were enrolled and liver cyst indicators were assessed based on mutation type (truncating mutation: nonsense, frameshift, and splicing mutation; non-truncating mutation: substitution) and mutation position. Liver cyst severity was determined using Gigot and Drenth classifications, based on their number, maximum diameter, and area ratio with the liver. Results We observed an overall prevalence of 62.8% for polycystic liver disease. Patients with PKD1 nonsense mutations, a type of PKD1 truncating mutation, exhibited more severe liver disease phenotypes than those without the mutation. We identified maximum diameter as a potential liver cyst indicator. Moreover, a subgroup analysis that included a PKD1 nonsense mutation cohort revealed that genetic mutations located closer to the 5MODIFIER LETTER PRIME end of PKD1 were associated with a maximum diameter index value >= 6 cm. Conclusion PKD1 nonsense mutations were associated with liver cyst severity, which along with maximum diameter index as a simple clinical indicator for liver cysts, may improve the treatment of polycystic liver disease associated with ADPKD.