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. 2017 Aug 1;10(8):8709-8714.
eCollection 2017.

Long-term follow-up of an Alport syndrome patient with a novel mutation of COL4A5

Rong Xiang  1 , Jing-Jing Li  1 , Ji-Shi Liu  2 , Liang-Liang Fan  1 , Lin Li  2 , Kun Xia  1 , Hao Zhang  2
Affiliations

Long-term follow-up of an Alport syndrome patient with a novel mutation of COL4A5

Rong Xiang et al. Int J Clin Exp Pathol. .

Abstract

Background: Alport syndrome (AS) is a genetic disease characterized by progressive glomerulonephritis with a high life-time risk for end-stage renal disease (ESRD), sensorineural hearing loss and ocular abnormalities. So far, a lot of mutations were reported in COL4A3, COL4A4 and COL4A5 genes, which are related to AS.

Methods: Whole-exome sequencing in combination with AS-related genes filtering strategy was applied to investigate a Chinese AS family. We also employed Sanger sequencing to confirm the family co-segregation. In addition, we also summed up a long-term follow-up data from 2003 to 2016.

Results: In this study, we have detected a novel insertion mutation (c.348_349insTCCGG/p.G117Sfs×40) of COL4A5, which may lead to a truncated protein in the proband. Sanger sequencing confirmed that this novel mutation was co-segregated with all the family members. The long-term follow-up data showed that the progress of chronic kidney disease become more and more serious in the proband.

Conclusions: A novel mutation (c.348_349insTCCGG/p.G117Sfs×40) of COL4A5 was identified in this study. In addition, approximately 15 years long-term follow-up data was provided in this paper. Our study not only expands the spectrum of COL4A5 mutations, but also analysis the progress of AS and fills the knowledge about course and potential further complications and health risks of AS.

Keywords: Alport syndrome; COL4A5; insertion mutation; long-term follow-up; whole-exome sequencing.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
A. Pedigree involved in this study, there were 15 numbers totally. □, male members; ○, female members; Mark 1, deceased male member who was affected by uremia; Mark 2, deceased affected female member with mild hematuria; Mark 3, affected female members with mild hematuria, who has the insertion mutation (c.348_349insTCCGG/G117Sfs*40); Mark 4, the proband; ■, affected male members who was diagnosed as typical Alport syndrome. B. Analysis of COL4A5. The chromatograms show partial sequence of COL4A5, c.348_349insTCCGG/G117Sfs*40, they are control, female patient and male patient. C. Conservation analysis of COL4A5. G117 sites are highlighted in blue. It is highly conserved at protein level across human, Ptroglodytes, Mmusculus, Trubripes, Drerio, Celegans, Xtropicalis, etc.
See this image and copyright information in PMC

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