Institute of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Medical Biology and Genetics, School of Medicine, University of Zagreb, Zagreb, Croatia.
Biomol Biomed. 2023 Feb 1;23(1):89-100. doi: 10.17305/bjbms.2022.7567.
Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 - 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients.
Alport 综合征（AS）和薄基底膜肾病（TBMN）是由Ⅳ型胶原α3、α4 或α5 链的致病变异引起的一系列肾脏疾病的一部分，Ⅳ型胶原是肾小球基底膜（GBM）的主要结构成分。通过靶向下一代测序（NGS），在 12 个无关家庭的 34 名 AS/TBMN 患者（58.8%为男性）中发现了 COL4A3 基因 c.2881+1G>A 杂合变异，该变异被认为是致病的。所有患者均来自克罗地亚大陆或岛屿部分。从病历中收集的临床、实验室和组织病理学数据进行了分析和比较，以了解受影响患者的临床过程和预后。在进行活检或首次临床评估时，平均年龄为 31 岁（中位数：35 岁；范围：1-72 岁）。33 名患者（97.1%）存在血尿，19 名患者（55.9%）存在蛋白尿。有 6 名（17.6%）患者有听力损失，4 名（11.8%）患者有眼部病变，11 名（32.4%）患者有高血压。23 名（67.6%）患者在随访时有蛋白尿，其中 5 名（14.7%）患者的中位年龄为 48 岁（范围：27-55），进展为肾衰竭，开始透析或接受了肾移植。在进行了肾脏活检的 13 名患者中，4 名（30.8%）出现局灶节段性肾小球硬化（FSGS），8 名（66.7%）出现 GBM 板层化，包括所有出现 FSGS 的患者。对每个Ⅳ型胶原遗传变异进行详细分析对于优化受影响患者的预后和治疗方法至关重要。
