Abstract: FR-PO615
A Case Report of a Novel Variant of X-Linked Alport Syndrome
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
- Gaeta, Robert M., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Yuan, Christina M., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Nee, Robert, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Thurlow, John Stephen, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction
X-linked Alport syndrome is a rare hereditary disorder caused by COL4A5 gene variants. We describe a case of a 28 year old Caucasian male with a family history of end-stage renal disease (ESRD) presenting with episodic gross hematuria and nephrotic range proteinuria. Renal biopsy showed focal segmental glomerulosclerosis with non-diagnostic ultrastructural findings. Next Generation Sequencing showed a COL4A5 missense likely pathogenic variant, substituting adenine for guanine at nucleotide 901(c.901G>A) of coding DNA predicting a glycine to serine substitution at amino acid 301 (p.Glyc301Ser).
Case Description
A 28 year-old Caucasian male with recent diagnosis of hypertension and a family history of ESRD presented with episodic gross hematuria and nephrotic range proteinuria (7.7g/g). Blood pressure was 146/92 mmHg. Physical examination was unremarkable with no lower extremity edema. All other laboratory testing and renal ultrasound was unremarkable. Renal biopsy showed FSGS with non-diagnostic ultrastructural findings (figure 2). NGS and Sanger Sequencing revealed a COL4A5 missense variant, substituing adenine for guanine at nucleotide 901(c.901G>A) of coding DNA predicting a glycine to serine substitution at amino acid 301 (p.Glyc301Ser).
Discussion
The pathogenicity for this novel missense variant is strongly suspected based on its location in a conserved GLY-Xaa-Yaa triple helical domain in the COL4A5 gene. Knebelmann et al first reported a similar missense variant substituting arginine for glycine at position 325 in a large kindred of X-linked Alport syndrome. The variant genotype has implications for individual prognosis. A study of 175 X-linked AS families showed that rate of progression of renal and extra-renal manifestations was associated with mutation type. Those with Gly-Xaa-Yaa variants reached ESRD at a median of 33 years versus 25 years for truncating mutations. Correct diagnosis allowed for appropriate genetic counseling and treatment, including ACE inhibitor therapy and the avoidance of immunosuppression.
The views expressed in this presentation are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of the Army, the Department of Defense, nor the US Government.