Abstract: FR-PO616
A New Pathogenic Stop Codon Variant in the COL4A5 Gene
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1002 Genetic Diseases of the Kidney: Non-Cystic
Authors
- Perez-Ledezma, Claudio, Indiana University School of Medicine, Division of Nephrology, Indianapolis, Indiana, United States
- Sharfuddin, Asif A., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Phillips, Carrie L., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Eadon, Michael T., Indiana University School of Medicine, Division of Nephrology, Indianapolis, Indiana, United States
Introduction
X-linked Alport syndrome (AS) is a progressive form of renal failure caused by pathogenic variants in the COL4A5gene. More than 702 variants have been described and a further 400 are estimated to be known to individual laboratories but have not been published.
Case Description
We present the case of a 30 year-old man with a history of AS diagnosed at age 8 years (hearing loss, vision deficit, and proteinuria) who presented for discussion of inheritance patterns of his disease as part of family planning with his current partner. AS was biopsy-proven at age 14 years, which showed thinned and multi-laminated glomerular basement membranes. He experienced an acute decline in renal function at age 22 years, requiring dialysis for 2 years before undergoing a living-related renal transplant. He and his significant other have no known family history of chronic kidney disease. He notes a history of hypertension in his maternal grandfather. Since a pedigree was not possible, it was unclear whether he had X-linked, autosomal recessive, or autosomal dominant inheritance. Thus, the patient underwent sequencing of COL4A3, COL4A4, COL4A5, and COL4A6 genes to determine his specific mutation. A hemizygous stop codon variant was found in exon 52 of the COL4A5 gene, designated c.4829C>A, resulting in premature protein termination (p.Ser1610*) after TCA to TAA conversion. He was referred for genetic counseling.
Discussion
About 65% of AS cases are caused by COL4A5mutations and are inherited in an X-linked pattern. The patient’s variant c.4829C>Aappears to be pathogenic in this given clinical context and has never been previously reported. The description and reporting of COL4A5 variants and clinical associations help to predict phenotype and understanding of collagen type IV biochemistry, which may ultimately inform therapy.