According to a study from Hindawi, a team of scientists have reported the discovery of never before seen mutations that are linked to Alport syndrome, a rare kidney disease. These mutations were identified in two Chinese families and were associated with significant differences in disease presentation between the males and females in the families. These findings have significant implications for genetic testing and diagnosis of Alport syndrome.

About Alport Syndrome

Alport syndrome is a genetic disorder which is characterized by end-stage kidney disease, hearing loss, and glomerulonephritis, a type of kidney disease in which the glomeruli or small blood vessels in the kidneys become inflamed. Alport syndrome is a heritable disease and is caused by mutations of the COL4A3, COL4A4, and COL4A5 genes. The symptoms of the disorder include blood and protein in the urine, leiomyomatosis (coughing, vomiting, bronchitis, stomach pain, dysphagia), various eye conditions, and, rarely, aortic dissection. Since kidney failure inevitably develops eventually, treatment is similar to that of chronic kidney disease, and patients will eventually require dialysis or a kidney transplant. ACE inhibitors appear to slow the decline of kidney function. There is a serious need for more effective treatments for this disorder. To learn more about Alport syndrome, click here.

Study Findings

The difference in symptoms between males and females is explained by the fact that Alport syndrome is triggered by X-linked mutations in around 80 percent of cases. In the first family that was evaluated, the new mutation was identified on exon 7 of the COL4A5 gene and was classified as a frameshift deletion mutation. This mutation was associated with end-stage kidney disease early in life for the male patients and microscopic hematuria as the only symptom that appeared in the females.

In the second family, the new mutation appeared on exon 9 and was classified as a missense mutation. The phenotype in this mutation was highly elevated serum creatinine in the male and hematuria in the female. These mutations were not present in any of the current databases checked by the researchers. A review of the literature found that earlier an study had associated COL4A5 missense and deletion mutations with a more severe presentation in men. Ultimately, the findings expand the mutational spectrum in this gene and should inform genetic screening and diagnosis of Alport syndrome going forward.