Kidney Week

Abstract: PUB170

Kidney-Limited FSGS Due to INF2 Mutation: A Neurologically Silent Case

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Hernandez Henriquez, Brenda Paola, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Brenda Paola Hernandez Henriquez, MD

• Arenas Lerma, Manuel Eduardo, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Manuel Eduardo Arenas Lerma, MD

• Olivo Gutierrez, Mara Cecilia, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Mara Cecilia Olivo Gutierrez, MD

• Frias Martinez, Ivana Daniela, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Ivana Daniela Frias Martinez

• Rizo Topete, Lilia Maria, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Lilia Maria Rizo Topete, MD

• Guerrero Gonzalez, Elisa Maria, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Elisa Maria Guerrero Gonzalez, MD

• Gomez Villarreal, Juan Pablo, Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, N.L., Mexico

Juan Pablo Gomez Villarreal, MD

Group or Team Name

• Centro Regional de Enfermedades Renales Roberto Gonzalez Barrera.

Introduction

It has been reported that genetic FSGS in adults ranges from 10%-43%, meaning that 57%-90% of adult cases may lack an identified genetic cause. In adults aged 19-25, a monogenic cause is found in 21.4% of cases. The most common autosomal dominant mutation is in INF2 in up to 17% of familial cases and linked to cytoskeletal remodeling. Pathogenic INF2 variants cause ~12% of familial and 1% of sporadic FSGS cases. The specific INF2: c.658A>G variant is restricted to FSGS.

Case Description

A 22-yo woman with no prior conditions and a maternal history of early no filiated CKD over two generations, presented with one month asthenia, weakness, and exertional dyspnea, without leg edema. Labs showed creatinine 10 mg/dL, proteinuria 3.8 g/vol, urine output 2100 ml, and albumin 3.2 g/dL. Ultrasound showed normal-sized kidneys, no structural changes. No hypertensive retinopathy; viral panel, C3, C4, and ANA were all normal/negative. Renal biopsy showed global and diffuse glomerulosclerosis, suggestive of FSGS. Genetic testing for kidney disease genes found a pathogenic INF2 variant: c.658G>A in heterozygous state.

Discussion

FSGS is a common cause of nephrotic syndrome and kidney failure, especially in young people. Its causes include secondary, idiopathic, and genetic forms. Among genetic types, INF2 variants are a leading cause of autosomal dominant FSGS, seen in up to 17% of familial cases. INF2 encodes a protein that regulates actin in podocytes. Its dysfunction disrupts slit diaphragm structure and function, leading to proteinuria and glomerular damage. Variants in exons 2–3, are also linked to CMT neuropathy, suggesting mixed phenotypes. This patient with INF2:c.658G>A (heterozygous) had advanced FSGS without neurologic symptoms. This variant has only been tied to kidney disease, supporting a restricted phenotype. This highlights the value of identifying specific INF2 mutations for diagnosis, prognosis, and family assessment.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ck8dczqa