COL4A3 mutations cause focal segmenta glomerulosclerosis  

作　　者：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 

机构地区：[1]Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]State Key Laboratory for Medical Genomics, Institute of Health Sciences, Shanghai ]iao Tong University School of Medicine (SJTUSM) and Shanghai Institutes forBiological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China [3]Nephrology Department, Huadong Hospital Affiliated to Fudan University, Shanghai, China [4]State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai, China [5]Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA

出　　处：《Journal of Molecular Cell Biology》2014年第6期498-505,共8页分子细胞生物学报（英文版）

基　　金：This workwas supported by grants from the National Basic Research Program of China 973, grant no. 2012CB517600 （no. 2012CB517604）, the National Natural Science Foundation of China （no. 81030015, 81070568, 81370015, and 81000295）, the International Cooperation and Exchange Projects of Shanghai Science and Technology Committee （no. 14430721000）, and the Chinese Medical Association Clinical Research Special Fund （no. 13030280413）.

摘　　要：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.

关 键 词：FSGS MUTATION COL4A3 COL4A4 

分 类 号：Q754[生物学—分子生物学] S856.59[农业科学—临床兽医学]