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. 2016 Aug;144(2):200-205.
doi: 10.4103/0971-5916.195026.

Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing

Sheng Deng  1 , Hongbo Xu  2 , Jinzhong Yuan  3 , Jingjing Xiao  4 , Lamei Yuan  2 , Xiong Deng  2 , Liping Guan  4 , Anding Zhu  2 , Pengfei Rong  5 , Jianguo Zhang  4 , Hao Deng  2
Affiliations

Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing

Sheng Deng et al. Indian J Med Res. 2016 Aug.

Abstract

Background & objectives: Alport syndrome (AS) is an inherited disorder characterized by glomerulonephritis and end-stage renal disease (ESRD). The aim of this study was to identify the gene responsible for the glomerulopathy in a Chinese family with autosomal dominant AS using exome sequencing.

Methods: A 4-generation, 30-member Chinese Han family was enrolled in this study. Exome sequencing was conducted in the proband of the family, and then direct sequencing was performed in family members of the pedigree and 100 normal controls.

Results: A novel frameshift mutation, c.3213delA (p.Gly1072GlufsFNx0169), in the collagen type IV alpha-4 gene (COL4A4) was found to be the genetic cause. Neither sensorineural hearing loss nor ocular abnormalities were present in the patients of this family. Other clinical features, such as age of onset, age of ESRD occurring and disease severity, varied among the patients of this family.

Interpretation & conclusions: A novel frameshift mutation, c.3213delA (p.Gly1072GlufsFNx0169) in the COL4A4 gene, was identified in the Chinese pedigree with autosomal dominant AS. Our findings may provide new insights into the cause and diagnosis of AS and also have implications for genetic counselling.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Pedigree of the family with autosomal dominant glomerulopathy. N, normal; M, collagen type IV alpha-4 c.3213delA mutation. Arrow indicates the proband.
Fig. 2
Fig. 2
Heterozygous c.3213delA mutation in the collagen type IV alpha-4 gene.
See this image and copyright information in PMC

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