Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families

• Published in: Human genome variation Vol. 5; no. 1; pp. 15 - 5
• Main Authors: Hines, Stephanie L., Agarwal, Anjali, Ghandour, Mohamedanwar, Aslam, Nabeel, Mohammad, Ahmed N., Atwal, Paldeep S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2018; Springer Nature B.V
• Subjects: 631/208/2489/1512; 692/699/1585/2759/1523; Biomedical and Life Sciences; Biomedicine; Gene Expression; Gene Function; Gene Therapy; Human Genetics; Molecular Medicine
• ISSN: 2054-345X; 2054-345X
• DOI: 10.1038/s41439-018-0016-8

We report two female patients with focal segmental glomerulosclerosis and chronic kidney disease. The first patient was found to have a heterozygous, de novo, pathogenic variant in COL4A5 (c.141+1G>A, IVS2+1G>A), which is associated with Alport syndrome. The second patient was found to have a heterozygous, likely pathogenic variant in COL4A4 (c.2842G>T). Both these variants in COL4A5 and COL4A4 are novel, and they were detected using whole exome sequencing and gene panel testing, respectively. Additionally, we discuss the complexities of diagnosis in such cases and the benefits of using the abovementioned diagnostic approaches. Kidney dysfunction: Identifying mutations linked with focal segmental glomerulosclerosis Researchers in the USA have identified two mutations linked with unrelated cases of the kidney disease focal segmental glomerulosclerosis (FSGS) and compared different diagnostic techniques. This disease is involved in roughly 40% of adult kidney dysfunction. Using sequencing of all protein-coding genes, Paldeep Atwal’s team at the Mayo Clinic, Jacksonville, identified a novel mutation in an FSGS patient. The mutation was not inherited, indicating that the patient’s siblings are not at increased risk. There were also mutations in other genes which may account for the patient’s vision loss. The team tested a second FSGS patient by screening kidney-related genes specifically, revealing a novel mutation in a different gene. Although the targeted approach is cheaper and quicker, these findings highlight the diagnostic benefits of full sequencing, which can reveal relevant mutations in unexpected genes.