A new mutation causing the autosomal dominant form of Alport syndrome has been identified in a Chinese family, a study published in the Indian Journal of Medical Research reports.
According to the researchers led by Dr. Hao Deng of Central South University, in Changsha, China, this finding may help in understanding the cause of, and in diagnosing, Alport syndrome, and have implications for genetic counseling.
“This study identified not only the genetic cause of glomerulopathy in the family studied but also two asymptomatic family members harbouring the same … mutation,” the scientists wrote in the report, titled “Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing.”
The team analyzed 30 members across four generations of a Chinese Han family, where seven men and three women had a kidney disease known as glomerulopathy.
Researchers performed exome sequencing (where all the genes in the genome that are expressed are analyzed) on one family member, a 32-year-old man with normal kidney function but who continuously had small amounts of blood in his urine.
In this way, they identified a new mutation in the COL4A gene, which causes Alport syndrome. This mutation (found in the collagen type IV alpha-4 gene, COL4A4) was not previously reported in the Chinese population, and the researchers did not encounter it in any of the 100 ethnically matched healthy volunteers they also analyzed.
Other family members were then assessed, and researchers found that 10 people with adult-onset Alport syndrome also carried the same mutation. Two of these family members had progressed to end-stage kidney disease and, beginning at ages 56 and 60, respectively, required dialysis.
Another two family members, brothers ages 8 and 11 and without disease symptoms, also carried the mutation. The researchers thought the absence of the disease was likely due to their young age. No hearing loss or eye abnormalities were found in any members of the family.
Alport syndrome is caused by genetic defects in the type IV collagen, a structural protein common in the body and found in the kidneys, ears and eyes. There are six genes involved in the biosynthesis of type IV collagen, and mutations in any of them can cause problems in the production and assembly of type IV collagen and lead to Alport syndrome.