title: A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis.
abstract: 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.
authors.affiliation: 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.|Department of Clinical Laboratory, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: 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.|Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Pengzhi
authors.initials: P
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D024141:Collagen Type IV / Q000737:chemistry / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005190:Family; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree
chemical_list: C466620:COL4A4 protein, human; D024141:Collagen Type IV
keywords: collagen IV nephropathies; exome sequencing; focal segmental glomerulosclerosis; mutation; the COL4A4 gene