A novel COL4A4 gene variant (c.1856G>A): from a focal segmental glomerulosclerosis case to a family with Alport syndrome

Abstract

Alport syndrome, also known as hereditary nephritis, is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. It is caused by mutations in genes encoding several members of type IV colagen proteins primarily found in basement membranes. Genetic analyses of affected families have identified four different modes of transmission in patients with Alport syndrome. X-linked form of the syndrome arises from mutations of COL4A5 and COL4A6 on chromosome X, whereas autosomal forms result from genetic defects in either the COL4A3 or COL4A4 genes at chromosome 2q35-37. Digenic forms include patients with coexisting mutations in COL4A3, COL4A4, and COL4A5. The long-term clinical outcome in AS patients with heterozygous COL4A3/A4 mutations is generally unpredictable. Focal segmental glomerulosclerosis usually develops in classical AS at later stages and presents predominantly with proteinuria associated with hematuria. The index case presented in this report, a 26-year-old man, had kidney biopsy because of nephrotic proteinuria and microscopic hematuria accompanied by impaired renal function. He diagnosed focal segmental glomerulosclerosis. As he had progressive hearing loss since chidhood we conducted a genetic study for mutations in COL4A3 and COL4A4 genes. A novel mutation in COL4A4 gene (c.1804-7T>C) was detected. As his parents had consanguineous marriage we investigated the rest of the family for the same variant. His parents, and his sister were found to be heterozygote, and homozygote for the same variant, respectively. In this report we demonstrated an Alport syndrome family with a novel mutation in COL4A4 gene (c.1856G>A) that has been first reported to our best knowledge.

Keywords

• síndrome de Alport
• mutaciones COL4A4
• glomeruloesclerosis focal segmentaria