Cannarella Rossella, Bertelli Matteo, Condorelli Rosita A, Vilaj Marija, La Vignera Sandro, Jezek Davor, Calogero Aldo E
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
MAGI Euregio, Bolzano, Italy.
World J Mens Health. 2023 Apr;41(2):422-433. doi: 10.5534/wjmh.220009. Epub 2022 Jul 14.
To analyze the presence of potentially pathogenic variants of 29 candidate genes known to cause spermatogenic failure (SPGF) in patients with non-obstructive azoospermia (NOA) who underwent testicular histology.
Forty-eight patients with unexplained NOA referred to the Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb, Zagreb, Croatia for testicular biopsy. They were divided into three groups: those who had cryptorchidism (n=9), those with varicocele (n=14), and those with idiopathic NOA (n=25). All included patients underwent blood withdrawal for next-generation sequencing (NGS) analysis and gene sequencing.
We found a possible genetic cause in 4 patients with idiopathic NOA (16%) and in 2 with cryptorchidism (22%). No pathogenic or possibly pathogenic mutations were identified in patients with varicocele. Variants of undetermined significance (VUS) were found in 11 patients with idiopathic NOA (44%), 3 with cryptorchidism (33%), and 8 patients with varicocele (57%). VUSs of the gene were the most frequently as they were found in 14 out of 48 patients (29%). In particular, the VUS c.7434+14del was found in 11 patients. They showed varied histological pictures, including Sertoli cell-only syndrome, mixed atrophy, and hypospermatogenesis, regardless of cryptorchidism or varicocele. No direct correlation was found between the gene mutation/variant and the testicular histological picture.
Different mutations of the same gene cause various testicular histological pictures. These results suggest that it is not the gene itself but the type of mutation/variation that determines the testicular histology picture. Based on the data presented above, it remains challenging to design a genetic panel with prognostic value for the outcome of testicular sperm extraction in patients with NOA.
分析29个已知可导致生精功能障碍（SPGF）的候选基因的潜在致病变异在接受睾丸组织学检查的非梗阻性无精子症（NOA）患者中的存在情况。
48例不明原因的NOA患者转诊至克罗地亚萨格勒布大学医院中心输血医学与移植生物学系进行睾丸活检。他们被分为三组：隐睾患者（n = 9）、精索静脉曲张患者（n = 14）和特发性NOA患者（n = 25）。所有纳入的患者均接受采血以进行下一代测序（NGS）分析和基因测序。
我们在4例特发性NOA患者（16%）和2例隐睾患者（22%）中发现了可能的遗传原因。精索静脉曲张患者未发现致病或可能致病的突变。在11例特发性NOA患者（44%）、3例隐睾患者（33%）和8例精索静脉曲张患者（57%）中发现了意义未明的变异（VUS）。该基因的VUS最为常见，在48例患者中有14例（29%）被发现。特别是，VUS c.7434+14del在11例患者中被发现。无论有无隐睾或精索静脉曲张，他们都表现出不同的组织学图像，包括唯支持细胞综合征、混合性萎缩和精子发生低下。未发现基因突变/变异与睾丸组织学图像之间存在直接相关性。
同一基因的不同突变会导致各种睾丸组织学图像。这些结果表明，决定睾丸组织学图像的不是基因本身，而是突变/变异的类型。基于上述数据，为NOA患者设计具有预测睾丸精子提取结果预后价值的基因检测板仍然具有挑战性。
