Abstract: FR-PO0132
Beyond the X Chromosome: Early-Onset FSGS in a Female Patient Associated with a TBC1D8B Variant Identified by Whole-Genome Sequencing
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Khambati, Ibrahim, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Bobart, Shane A., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Aslam, Nabeel, Mayo Clinic in Florida, Jacksonville, Florida, United States
Introduction
Pathogenic variants in TBC1D8B, an X-linked gene involved in podocyte function, are a rare cause of steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FSGS), predominantly affecting males. Female presentations are exceedingly uncommon, with only two reported cases. We describe the youngest reported female with nephrotic syndrome and biopsy-proven FSGS associated with a TBC1D8B variant identified through whole genome sequencing.
Case Description
A 19-year-old woman with no family history of kidney disease presented with edema, hypoalbuminemia, hyperlipidemia, and nephrotic-range proteinuria following an upper respiratory infection. Kidney biopsy demonstrated FSGS with diffuse podocyte foot process effacement, negative immunofluorescence, and minimal chronicity. Secondary evaluation, including hepatitis B/C, HIV, autoimmune serologies, and medication review, was unrevealing. Corticosteroids failed to induce remission, and proteinuria worsened during taper, prompting tacrolimus initiation with limited response. Proteinuria persisted (urine protein-creatinine ratio 2.7–3 g/g) with serum albumin ~3.1 g/dL. Given steroid resistance, genomic evaluation was pursued. Natera Renasight (targeted kidney disease gene panel) was negative; however, whole genome sequencing identified a pathogenic TBC1D8B variant. In contrast to typical male phenotypes, our female patient developed significant disease at a younger age despite the absence of a family history. Given poor response to immunosuppression, the presentation was considered genetic FSGS, and tacrolimus was tapered while continuing lisinopril and dapagliflozin.
Discussion
This case expands the phenotypic spectrum of TBC1D8B-associated nephropathy by demonstrating early-onset FSGS in a female, representing only the third reported case and the youngest to date. While prior reports describe adult-onset disease in females, this case supports variable penetrance. A potential mechanism is skewed X-chromosome inactivation, leading to preferential expression of the mutant allele in podocytes and a functional hemizygous state. This highlights the importance of considering monogenic causes in young patients with steroid-resistant FSGS. Advanced genomic testing can clarify diagnosis, guide prognosis, and avoid prolonged ineffective immunosuppression.