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. 2016 Dec;20(12):2328-2332.
doi: 10.1111/jcmm.12924. Epub 2016 Jul 29.

A Novel Heterozygous COL4A4 Missense Mutation in a Chinese Family With Focal Segmental Glomerulosclerosis

Free PMC article

A Novel Heterozygous COL4A4 Missense Mutation in a Chinese Family With Focal Segmental Glomerulosclerosis

Yuan Wu et al. J Cell Mol Med. .
Free PMC article


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.

Keywords: collagen IV nephropathies; exome sequencing; focal segmental glomerulosclerosis; mutation; the COL4A4 gene.


Figure 1
Figure 1
Pedigree and sequence analysis of an FSGS family. (A) Pedigree of the family with FSGS. N: normal; M: the COL4A4 c.1856G>A (p.Gly619Asp) variant. Arrow indicates the proband. (B) Sequence of heterozygous c.1856G>A (p.Gly619Asp) variant. (C) Sequence of a normal control. FSGS: Focal segmental glomerulosclerosis.
Figure 2
Figure 2
Conservation analysis of the collagen type IV α4 chain p.Gly619 amino acid residue.

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