De Novo SALL-1 Gene Mutation Associated with Immune-Suppressive-Resistant FSGS and Recurrent Kidney Stones: A Case Report

Introduction: The SALL1 gene, located on chromosome 16, encodes a zinc finger transcription factor that plays a crucial role in kidney development and ciliary function. Mutations in this gene have been associated with various pathological conditions. Renal involvement can manifest in several ways, including abnormalities of the urogenital tract, dysplastic kidneys, and glomerular diseases such as focal segmental glomerulosclerosis (FSGS). This report presents the first documented case of refractory FSGS linked to a SALL1 gene mutation in the adult Saudi population. Case Description: A 42-year-old male with a history of recurrent kidney stones presented with Shortness of breath and was found to have pulmonary embolism in the setting of nephrotic syndrome. Initial investigations revealed a creatinine of 134 micromol/L, a serum albumin level of 22.2 g/L, and a 24-hour urine protein of 11.6 grams. A kidney biopsy found focal segmental glomerulosclerosis mainly at the tip domain. Immunosuppressive therapy with prednisone failed to induce remission. Our patient was subsequently started on tacrolimus, followed by rituximab, with no response. Genetic testing was positive for a SALL1 gene mutation, with no family history of kidney disease or associated syndromes. Audiometry assessment was unremarkable, and magnetic resonance imaging revealed a bifid right renal pelvis with narrowing at the pelvi-ureteric junction. Discussion: In our patient, the presence of urogenital tract anomalies followed by the diagnosis of focal segmental glomerular sclerosis at age 41 highlights the heterogeneity of presentations of this syndrome. Identifying this condition is crucial to prevent unnecessary immunosuppression and to provide genetic counseling for relatives and offspring. Further studies are needed to describe the role of SALL1 gene mutations in different kidney diseases.