Department of Gastroenterology and Hepatology, Research Institute for Medical Innovation, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
European Reference Network RARE-LIVER, D-20246 Hamburg, Germany.
Genes (Basel). 2023 Sep 2;14(9):1755. doi: 10.3390/genes14091755.
α-1,2-mannosyltransferase () germline variants are linked to autosomal dominant polycystic kidney disease (ADPKD). Many individuals affected with ADPKD possess polycystic livers as a common extrarenal manifestation. We performed whole exome sequencing in a female with autosomal dominant polycystic liver disease (ADPLD) without kidney cysts and established the presence of a heterozygous missense variant (c.677G>C p.(Gly226Ala)) in . In silico pathogenicity prediction and 3D protein modeling determined this variant as pathogenic. Loss of heterozygosity is regularly seen in liver cyst walls. Immunohistochemistry indicated the absence of ALG9 in liver tissue from this patient. ALG9 expression was absent in cyst wall lining from - and -caused ADPLD patients but present in the liver cyst lining derived from an ADPKD patient with a variant. Thus, heterozygous pathogenic variants in are also associated with ADPLD. Somatic loss of heterozygosity of the ALG9 enzyme was seen in the patient but also in ADPLD patients with a different genetic background. This expanded the phenotypic spectrum of ADPLD to .
α-1,2-甘露糖基转移酶 () 种系变异与常染色体显性多囊肾病 (ADPKD) 相关。许多患有 ADPKD 的个体还表现出多囊性肝病，这是一种常见的肾脏外表现。我们对一名无肾脏囊肿的常染色体显性多囊性肝病 (ADPLD) 女性进行了全外显子组测序，并在 中发现了一个杂合错义变异 (c.677G>C p.(Gly226Ala))。体外致病性预测和 3D 蛋白建模确定该变体具有致病性。杂合性丢失在肝囊肿壁中经常见到。免疫组织化学显示该患者的肝组织中不存在 ALG9。在由 - 和 - 引起的 ADPLD 患者的肝囊肿壁衬里中不存在 ALG9 表达，但在源自具有 变异的 ADPKD 患者的肝囊肿衬里中存在。因此， 中的杂合致病性变异也与 ADPLD 相关。ALG9 酶的杂合性缺失在该患者中可见，也在具有不同遗传背景的 ADPLD 患者中可见。这将 ADPLD 的表型谱扩展到了 。
