Wu Yuan, Hu Pengzhi, Xu Hongbo, Yuan Jinzhong, Yuan Lamei, Xiong Wei, Deng Xiong, Deng Hao
Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
J Cell Mol Med. 2016 Dec;20(12):2328-2332. doi: 10.1111/jcmm.12924. Epub 2016 Jul 29.
Focal segmental glomerulosclerosis (FSGS) is the most common glomerular histological lesion associated with high-grade proteinuria and end-stage renal disease. Histologically, FSGS is characterized by focal segmental sclerosis with foot process effacement. The aim of this study was to identify the disease-causing mutation in a four-generation Chinese family with FSGS. A novel missense mutation, c.1856G>A (p.Gly619Asp), in the collagen type IV alpha-4 gene (COL4A4) was identified in six patients and it co-segregated with the disease in this family. The variant is predicted to be disease-causing and results in collagen IV abnormalities. Our finding broadens mutation spectrum of the COL4A4 gene and extends the phenotypic spectrum of collagen IV nephropathies. Our study suggests that exome sequencing is a cost-effective and efficient approach for identification of disease-causing mutations in phenotypically complex or equivocal disorders. Timely screening for COL4A3/COL4A4 mutations in patients with familial FSGS may help both accurately diagnose and treat these patients.
局灶节段性肾小球硬化（FSGS）是与重度蛋白尿和终末期肾病相关的最常见的肾小球组织学病变。在组织学上，FSGS的特征是局灶节段性硬化伴足突消失。本研究的目的是在一个四代中国FSGS家系中鉴定致病突变。在六名患者中鉴定出了IV型胶原α-4基因（COL4A4）中的一个新的错义突变，c.1856G>A（p.Gly619Asp），并且该突变在这个家系中与疾病共分离。该变异预计会导致疾病，并导致IV型胶原异常。我们的发现拓宽了COL4A4基因的突变谱，并扩展了IV型胶原肾病的表型谱。我们的研究表明，外显子组测序是一种在表型复杂或不明确的疾病中鉴定致病突变的经济高效的方法。对家族性FSGS患者及时进行COL4A3/COL4A4突变筛查可能有助于准确诊断和治疗这些患者。
