Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy.
Prenatal Diagnosis Unit, Department of Obstetrics and Gynecology, ASST-Spedali Civili, Brescia, Italy.
J Nephrol. 2022 Mar;35(2):645-652. doi: 10.1007/s40620-021-01131-w. Epub 2021 Aug 6.
Causative mutations in the GANAB gene have been described in only 14 families, 9 diagnosed with late-onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) and 5 with Autosomal Dominant Polycystic Liver Disease (ADPLD).
Diagnosis of ADPKD was made in a 45-year old man during screening for hernia repair. CT scan showed enlarged cystic kidneys, nephrolithiasis and normal-sized liver with multiple cysts. Hematuria, hypertension and aortic root dilatation were also documented. Renal function was normal. Molecular analysis of PKD genes disclosed a heterozygous p.R839W GANAB variant inherited from the mother. Both his elderly parents presented normal-sized bilateral cystic kidneys but normal renal function. The GANAB-ADPKD mother had no liver cysts. The father was screened for PKD-related genes and no variant was found.
We describe a new family with late-onset ADPKD due to the p.R839W GANAB variant, previously reported in a severe ADPLD patient, requiring liver transplantation.
Since ADPKD-GANAB is an ultrarare, recently described disease, reporting further patients may help unraveling gene-related phenotype. In our patients the p.R839W GANAB variant was not related to severe ADPLD, as previously reported, but with mild ADPKD and a plethora of renal and extrarenal manifestations, usually described in PKD1/PKD2 patients. The evidence that the GANAB variant may cause both ADPKD and ADPLD of variable severity supports that renal and hepatic cystogenesis are the result of a common defective polycystin-1 pathway.
GANAB 基因的致病突变仅在 14 个家族中被描述过，其中 9 个家族被诊断为迟发性常染色体显性多囊肾病（ADPKD），5 个家族为常染色体显性多囊肝疾病（ADPLD）。
在疝修补术筛查过程中，一名 45 岁男性被诊断为 ADPKD。CT 扫描显示囊性肾脏增大、肾结石和正常大小的肝脏多发性囊肿。还记录了血尿、高血压和主动脉根部扩张。肾功能正常。PKD 基因的分子分析显示，该患者从母亲遗传到杂合的 p.R839W GANAB 变体。他的年长父母均表现为双侧囊性肾脏正常大小但肾功能正常。GANAB-ADPKD 母亲没有肝囊肿。父亲接受了 PKD 相关基因筛查，未发现变异。
我们描述了一个新的家族，该家族因 p.R839W GANAB 变体导致迟发性 ADPKD，该变体之前在一名需要进行肝移植的严重 ADPLD 患者中被报道过。
由于 ADPKD-GANAB 是一种极其罕见的、最近才被描述的疾病，因此报告更多的患者可能有助于揭示与基因相关的表型。在我们的患者中，p.R839W GANAB 变体与之前报道的严重 ADPLD 无关，而是与轻度 ADPKD 以及大量肾脏和肾脏外表现有关，这些表现通常在 PKD1/PKD2 患者中被描述。该 GANAB 变体可能导致 ADPKD 和 ADPLD 两种疾病且严重程度不同的证据表明，肾脏和肝脏囊肿的形成是共同的缺陷多囊蛋白-1 途径的结果。
