New Gene Mutation in Alport Syndrome Identified in Chinese Family

Researchers in China identified a new mutation causing Alport syndrome. This knowledge can help improve physicians diagnose the condition in the future.

Using a technique called targeted next generation sequencing (NGS), the team of researchers, led by Dr. Xue Zhang, demonstrated that a letter substitution in the DNA code from C to A causes a section in the middle of the COL4A5 gene not to be read. This results in a shorter than normal alpha-5 chain of type IV collagen, which the gene encodes, and may affect the three-dimensional formation or flexibility of collagen molecules, leading to symptoms of Alport syndrome.

“Our results indicated that targeted NGS can be a very powerful tool in high-throughput genetic testing of inherited diseases,” wrote the authors of the study “A Novel Splicing Mutation Identified in a Chinese Family with X-linked Alport Syndrome Using Targeted Next-Generation Sequencing.” It was published in the scientific journal Genetic Testing and Molecular Biomarker.

The study was based on the case of a Chinese family with X-linked Alport syndrome. Many individuals in the family were affected by the condition. A kidney specialist diagnosed the disease based on clinical findings and lab tests. Researchers then collected blood from available family members and performed genomic DNA analysis as well as expressed DNA analysis.

The first member of the family who was genetically analyzed was a 26-year-old man who first had blood in his urine at the age of 7. By the time he was 24 years old, he had protein in the urine, a sign of compromised kidney function and high blood pressure. A year later, he developed end-stage kidney disease and received a kidney transplant. His mother did not show any symptoms of the disease.

Genetic analysis revealed a C to A substitution in the COL4A5 gene of the 26-year old man. COL4A5 is situated on the X-chromosome and provides information to make alpha-5 chain of type IV collagen. The man’s mother had one healthy copy and one mutated copy of the COL4A5 gene, while his father had the healthy copy of the gene.

The researchers then demonstrated that the mutation led to a shorter transcript, or message from the gene, which could only code for a shorter type IV collagen alpha-5 chain.

This is the first report of the novel C to A substitution in the COL4A5 gene, adding to the spectrum of Alport syndrome-causing genetic mutations.