Abstract: TH-PO0388
A Novel ANLN Variant (p.Lys491Asn) with Incomplete Penetrance: Expanding the Phenotypic Spectrum to Minimal Change Disease in an Indian Pedigree
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Jain, Apoorva, SN Medical College, Agra, UP, India
- Mohan, Anurag, SN Medical College, Agra, UP, India
- Khurana, Mudit, SN Medical College, Agra, UP, India
- Bhardwaj, Kairavi, SN Medical College, Agra, UP, India
- Singh, Manish Kumar, SN Medical College, Agra, UP, India
- Kumar, Aditya, SN Medical College, Agra, UP, India
- Mehta, Astitva, SN Medical College, Agra, UP, India
Introduction
ANLN encodes anillin,protein essential for podocyte cytoskeleton and slit diaphragm achitecture. Heterozygous ANLN variants cause autosomal dominant FSGS8 (OMIM #616032), a rare podocytopathy linked to proteinuria/SRNS. First reported in 2014, fewer than 15 unrelated cases exist by 2026. Most show FSGS, age dependent onset, incomplete penetrance with variable phenotype. We report the first Indian father-son pair with identical novel ANLN missense variant showing reduced penetrance with surprisingly MCD histology in the child, and excellent tacrolimus response.
Case Description
A 2-year-old Indian boy (Master X) presented November 14, 2025, with 10-day generalized edema, nephrotic syndrome (albumin 2.2 g/dL, cholesterol 324 mg/dL, UACR 3612 mg/g). Steroid-resistant after 8 weeks. Renal biopsy (Jan 21, 2026) showed minimal change disease (MCD): normal light microscopy, negative IF, >80% foot process effacement on EM. Tacrolimus (0.5 mg BID, trough 5.3 ng/mL) led to complete remission by the end of week 3 (UACR 31.42 mg/g).
Renal NGS revealed heterozygous ANLN variant c.1473G>C; p.Lys491Asn (VUS). Identical variant found in asymptomatic 29-year-old father (normotensive, without proteinuria). Mother was found negative for this variant on renal NGS.
Discussion
This first Indian father-son case of ANLN c.1473G>C shows incomplete penetrance: child had early SRNS with MCD, father was asymptomatic at 29 year of age. Highlights histological MCD (not FSGS) in ANLN podocytopathy and prompt tacrolimus response via actin cytoskeleton stabilization. Genetic SRNS may not show FSGS on biopsy.