Abstract: SA-PO563
Podocalyxin (PODXL) Nonsense Variant in Patients With Atypical Adult-Onset Focal Segmental Glomerulosclerosis (FSGS)
Session Information
- Genetic Diseases: Diagnosis
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Arnaldi, Monica, Western University, London, Ontario, Canada
- Connaughton, Dervla M., Western University, London, Ontario, Canada
Group or Team Name
- Nephrology Division at Schulich School of Medicine & Dentistry, Western University
Introduction
Genetic kidney disease has been the focus of many investigative efforts, particularly in patients with adult-onset chronic kidney disease (CKD) and positive family history. FSGS is a podocyte-driven disease, that is the most frequent cause of CKD worldwide and regularly progresses to end-stage kidney disease (ESKD). The PODXL-encoded podocalyxin is a podocyte protein and a member of the CD34 family of stem cell sialomucins. It has recently been described in families with both recessive (compound heterozygous variants) and dominant forms of familial nephropathies. We detected a novel heterozygous nonsense variant in the PODXL gene c.1048C>T, p.(Arg350*).in a family with atypical FSGS.
Case Description
We detected a novel heterozygous nonsense variant in the PODXL gene c.1048C>T, p.(Arg350*) in a family with atypical FSGS. This variant was segregated in this family with 3 affected individuals with CKD all carrying the same variant.
The patient is a 43-year-old woman, who was first diagnosed 29 years with proteinuria, peripheral edema, and normal creatinine level. A kidney biopsy raised the suspicion of FSGS with patchy podocyte effacement but no definite segmental sclerotic glomerular lesions were identified. , There were some areas of thickening of the glomerular basement membranes and mild tubular atrophy and interstitial fibrosis. Initially, she commenced prednisone but had no response, treatment switched to mycophenolate but no response, then started on cyclosporine with low dose prednisone with a complete response followed by relapse. She was later switched to tacrolimus with partial response.
Discussion
Next-generation sequencing (NGS) technology can reveal the underlying etiology of disease in patients, where other diagnostic strategies have failed to confirm the diagnosis. In this case, histopathology following kidney biopsy raised the suspicion of FSGS but diagnosis could not be confirmed. Increased utilization of NGS is expected to increase diagnostic efficiency in patients with CKD, especially in patients with positive family history and/or young-onset ESKD. A definitive genetic diagnosis has important prognostic value to help understand these atypical subtypes of disease which may in turn impact treatment strategies for patients carrying particular genetic variants.