COL4A3 mutations cause focal segmenta glomerulosclerosis

• Published in: 分子细胞生物学报：英文版 2014 (6), p.498-505
• Main Author: Jingyuan Xie Xiaoxi Wu Hong Ren Weiming Wang Zhaohui Wang Xiaoxia Pan Xu Hao Jun Tong Jun Ma Zhibin Ye Guoyu Meng Yufei Zhu Krzysztof Kiryluk Xiangyin Kong Landian Hu Nan Chen
• Format: Article
• Language: English
• Subjects: 中国人群; 全身性疾病; 分割; 基因突变; 电子显微镜; 硬化; 肾功能衰竭; 肾小球
• ISSN: 1674-2788; 1759-4685

Focal segmental glomerulosclerosis （FSGS） is a histologically identifiable gtomerular injury often leading to proteinuria and renal failure. To identify its causal genes, whole-exome sequencing and Sanger sequencing were performed on a large Chinese cohort that comprised 40 FSGS families, 50 sporadic FSGS patients, 9 independent autosomal recessive Atport＇s syndrome （ARAS） patients, and 190 ethnically matched healthy controls. Patients with extrarenal manifestations, indicating systemic diseases or other known hereditary renal diseases, were excluded. Heterozygous COL4A3 mutations were identified in five （12.5%） FSGS families and one （2%） sporadic FSGS patient. All identified mutations disrupted highly conserved protein sequences and none of them was found in either public databases or the 190 healthy controls. Of the FSGS patients with heterozygous COL4A3 mutations, segmental thinning of the glomerular base membrane （GBM） was only detected in the patient with electronic microscopy examination results available. Five ARAS patients （55.6%） had homozygous or compound-heterozygous mutations in COL4.43 or COL4A4. Serious changes in the G BM, hearing loss, and ocular abnormalities were found in 100%, 80%, and 40% of the ARAS patients, respectively. Overall, a new sub- group of FSGS patients resulting from heterozygous C01.4A3 mutations was identified. The mutations are relatively frequent in famiUes diagnosed with inherited forms of FSGS. Thus, we suggest screening for C01.4A3 mutations in familial FSGS patients.