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Kidney Week

Abstract: FR-PO797

Reassessing the Pathogenicity of p.G953V in COL4A5 Gene: Report of 19 Chinese Families

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Zhang, Yanqin, Peking University First Hospital, Beijing, China
  • Wang, Fang, Peking University First Hospital, Beijing, China
Background

X-linked Alport syndrome (XLAS) is an inherited renal disease caused by mutations in COL4A5 gene. The p.G953V variant in COL4A5 gene is considered pathogenic previously. However, there is conflicting of its pathogenicity recently. Here we reported 19 Chinese families with the p.G953V in COL4A5 to evaluate its pathogenicity.

Methods

Families were selected from the on-line registry database of hereditary kidney diseases in children in China, according to the following two criteria a) cases with gene mutations tested by targeted next generation sequencing (NGS); b) cases with the p.G953V in COL4A5. The clinical data and genetic findings were collected and analyzed.

Results

Fifty-one individuals from 19 families were enrolled, out of which 36 (18 probands and 18 family members) carried p.G953V. We found there were no clinical features of XLAS not only in the 6 probands with p.G953V and pathogenic variants in other genes (e.g. WT1, ADCK4, NPHP1, TRPC6, COL4A4 and PAX2) but also in another 6 probands with only the p.G953V. The other 6 probands, with a combination of p.G953V and another pathogenic variant in COL4A5 had XLAS. Eleven family members (11/18, 9 females and 2 males) who had the p.G953V variant only were asymptomatic. These two males had normal result of urine analysis (at age of 42 and 35 years) and no more clinical traits of Alport syndrome.

Conclusion

The p.G953V in COL4A5 gene is not a pathogenic mutation for XLAS. Individuals should not be diagnosed as XLAS only based on the detection of p.G953V in COL4A5 gene.