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. 2019 Jul;7(7):e00741.
doi: 10.1002/mgg3.741. Epub 2019 May 29.

Genotype-phenotype correlation and prognostic impact in Chinese patients with Alport Syndrome

Shunlai Shang  1 , Fei Peng  1   2 , Tao Wang  1 , Xiaoyuan Wu  1 , Ping Li  1 , Qinggang Li  1 , Xiang M Chen  1
Affiliations

Genotype-phenotype correlation and prognostic impact in Chinese patients with Alport Syndrome

Shunlai Shang et al. Mol Genet Genomic Med. 2019 Jul.

Abstract

Background: Alport Syndrome (AS) is a progressive hereditary glomerular disease. It is often accompanied by sensorineural hearing loss and ocular abnormalities and can sometimes develop into end stage renal disease (ESRD), which is caused by mutations in the genes encoding the collagen type IV family of proteins.

Methods: This study analyzed the association between the clinical data of seven AS families and genes and the disease progression of different mutation types, including COL4A3 (OMIM 120070)，COL4A4 (OMIM 120131), and COL4A5 (OMIM303630).

Results: A total of six new pathogenic mutation sites, one complex heterozygous mutation at COL4A3, and a combined mutation of COL4A5 and INF2 (OMIM 610982) were identified in this study. It was revealed that the clinical manifestations of X-linked AS caused by mutations in the COL4A5 gene were more severe in males than in females. In addition, the difference in patient phenotype can be attributed to the location of gene mutations affecting the protein domain or functional domain. Our data suggested that the gene deletion and nonsense mutations had a high risk for progression to ESRD.

Conclusion: Our results revealed the spectrum of type IV collagen genes, which contribute to the enrichment of database resources and has important implications in the diagnosis, prognosis, and guiding treatment of AS.

Keywords: Alport Syndrome; Genotype-phenotype correlation; prognostic impact.

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Conflict of interest statement

The authors declare they have no conflict of interest.

Figures

Figure 1
Figure 1
(a) Pedigrees and COLA5 re‐sequencing chromatograms（family 1 and family 2. Arrows point to the mutations. Family 1 has one novel mutations, c.443C > T in the figure 1a;#, INF2 re‐sequencing chromatograms of Family 2. (b) Pedigrees and COLA5 re‐sequencing chromatograms. Arrows point to the mutations （family 3, family 4, and family 5）. Family 3 has one novel mutations, c.2366_2383del in the figure 1b; Family 5 has one novel mutations, c.4473T > A in the figure 1b
Figure 2
Figure 2
Pedigrees and COLA3 re‐sequencing chromatograms (family 6). Arrows point to the mutations. Family 6 has two novel mutations, c.971G > A and c.4411_4412del
Figure 3
Figure 3
Pedigrees and COLA4 re‐sequencing chromatograms (family 7). Arrows point to the mutations. Family 7 has one novel mutation, c. 3,782 G > A
See this image and copyright information in PMC

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