Zhu Fengming, Li Yueqiang, Wang Yuxi, Yao Ying, Zeng Rui
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2023 May 31;14:1180149. doi: 10.3389/fgene.2023.1180149. eCollection 2023.
Mutations in the collagen components of the glomerular basement membrane (GBM) often lead to hereditary glomerulonephritis. Previous studies have identified that autosomal dominant mutations of or are associated with thin basement membrane nephropathy (TBMN), Alport syndrome and other hereditary kidney diseases. However, the genetic mutations underlying other glomerulonephritis types have not been elucidated. In this study, we investigated a Chinese family with hereditary nephritis using the methods of genetic sequencing and renal biopsy. Genomic DNA was extracted from peripheral blood of the proband and her sister, and subsequently was performed genetic sequencing. They were found to have the similar mutation sites. Other family members were then validated using Sanger sequencing. The proband and her sister underwent renal puncture biopsies, and experienced pathologists performed PAS, Masson, immunofluorescence, and immunoelectron microscopic staining of the kidney tissue sections. Through genetic sequencing analysis, we detected a novel heterozygous frameshift mutation c.1826delC in the (NM_000092.4) gene coding region, and 1 hybrid missense variation c.86G>A (p. R29Q) was also detected in the (NM_019105.6) gene coding region in several members of this Chinese family. Interestingly, we found that the same mutations caused different clinical features and distinct pathological changes in individual family members, which confirmed that pathological and genetic testing are crucial for the diagnosis and treatment of hereditary kidney diseases. In this study, we found a novel heterozygous mutation in and co-mutations of the gene in this Chinese family. Our study indicated that the same mutated variants produced different pathological and clinical changes in different family members. This discovery may provide novel insights into the study of hereditary kidney disease. In addition, new genetic biology techniques and renal biopsy of individual family members are essential.
肾小球基底膜（GBM）胶原成分的突变常导致遗传性肾小球肾炎。先前的研究已确定，[具体基因1]或[具体基因2]的常染色体显性突变与薄基底膜肾病（TBMN）、Alport综合征及其他遗传性肾脏疾病相关。然而，其他类型肾小球肾炎的基因突变尚未阐明。在本研究中，我们采用基因测序和肾活检方法，对一个中国遗传性肾炎家系进行了调查。从先证者及其妹妹的外周血中提取基因组DNA，随后进行基因测序。发现她们有相似的突变位点。然后使用桑格测序法对其他家庭成员进行验证。先证者及其妹妹接受了肾穿刺活检，经验丰富的病理学家对肾组织切片进行了PAS、Masson、免疫荧光和免疫电镜染色。通过基因测序分析，我们在[具体基因1]（NM_000092.4）基因编码区检测到一个新的杂合移码突变c.1826delC，并且在这个中国家系的几个成员的[具体基因2]（NM_019105.6）基因编码区还检测到1个杂合错义变异c.86G>A（p.R29Q）。有趣的是，我们发现相同的突变在个体家庭成员中导致了不同的临床特征和明显的病理变化，这证实了病理和基因检测对于遗传性肾脏疾病的诊断和治疗至关重要。在本研究中，我们在这个中国家系中发现了[具体基因1]的一个新的杂合突变以及[具体基因2]的共突变。我们的研究表明，相同的[具体基因1]突变变体在不同家庭成员中产生了不同的病理和临床变化。这一发现可能为遗传性肾脏疾病的研究提供新的见解。此外，新的遗传生物学技术和对个体家庭成员的肾活检至关重要。
