Scientists Identify Novel COL4A4 Gene Mutation Leading to Alport Syndrome

Researchers reported the case of a Chinese family who developed Alport syndrome due to a novel mutation in the COL4A4 gene, which was previously unknown to be associated with the disease.

Knowing which mutations within the COL4A4 gene lead to Alport syndrome brings valuable insight into the development of the condition, broadening the possibilities for patient diagnosis, prognosis, and treatment.

The report, titled “Mutation analysis of COL4A3 and COL4A4 genes in a Chinese autosomal-dominant Alport syndrome family,” was published in the Indian Academy of Sciences’ Journal of Genetics.

Alport syndrome is mainly characterized by kidney failure due to mutations in the COL4 family of genes, including the COL4A4, COL4A3, and COL4A5 genes. These genes produce collagen proteins, which are expressed in the skin and in cells lining certain organs, such as kidneys. To date, only a few mutations in the COL4A4 and COL4A3 genes have been proven to lead to Alport syndrome.

The study reported the case of a 21-year-old Chinese man who went to the hospital complaining of facial swelling for the past month and a cough since two weeks prior. Examinations of the man’s blood and a kidney biopsy led doctors to a diagnosis of Alport syndrome.

The man’s 45-year-old uncle and 26-year-old sister had kidney hematuria (presence of blood in the urine) and proteinuria (presence of proteins in the urine), and mild hearing loss. Also, the patient’s father had undergone dialysis since the age of 60 and died of kidney failure at the age of 62.

Genetic tests performed with DNA samples from each patient revealed the presence of gene mutations within the COL4A4 gene. Namely, a variation known as c.4195 A>T (p.Met1399Leu) in this gene was found in all patients from this family.

“Results showed that the … variant was predicted to affect protein functions,” researchers wrote. “From this, we deduced that there was a high probability that the mutation Met1399Leu was the causative mutation of [Alport syndrome] in this family.”

“Our results broadened the spectrum of mutations in COL4A4 and had important implications in the diagnosis, prognosis and genetic counselling of [Alport syndrome],” researchers concluded.