SALL2 – Alport Syndrome

This summary evaluates the association between SALL2 (HGNC:10526) and Alport syndrome (MONDO:0018965) based on targeted exome sequencing studies in patients with complex renal phenotypes. In one case report, a novel deleterious SALL2 mutation was identified in a patient presenting with clinical features including hydronephrosis, recurrent urinary tract infections, nephrotic range proteinuria, focal segmental glomerulosclerosis, and microscopic hematuria (PMID:24130771).

Genetic evidence for SALL2’s role in Alport syndrome remains limited. Only a single proband with a reported deleterious SALL2 alteration was documented, and the mutation was detected in a background where well‐established COL4A3 variants were also present, ultimately confirming the clinical diagnosis. No additional unrelated probands or segregation data supporting the independent contribution of SALL2 were provided (PMID:24130771).

The variant spectrum for SALL2 in the context of Alport syndrome is not well established: no recurrent or founder mutations were reported and a valid HGVS string for SALL2 is not available from the current evidence. As such, the genetic evidence is insufficient to independently validate pathogenicity for renal malformation phenotypes.

Functional studies in other disease contexts have implicated SALL2 in processes such as neural tube closure, cell cycle regulation, and cell migration (PMID:18818376; PMID:24040083; PMID:29689621). However, these experimental data do not directly demonstrate a mechanism linking SALL2 dysfunction to the basement membrane pathology characteristic of Alport syndrome.

Integrating the available genetic and experimental findings, the association between SALL2 and Alport syndrome is rated as having limited clinical validity. While the discovery of a deleterious SALL2 mutation in a patient with Alport syndrome broadens the molecular spectrum of renal malformations, the sparse genetic data and lack of direct functional evidence for renal involvement suggest that further studies are needed.

Key take‑home: Although SALL2 may contribute to the genetic heterogeneity underlying renal malformations, its current clinical utility for diagnosing Alport syndrome remains limited and should be interpreted with caution.

References

• PLoS One • 2013 • Targeted exome sequencing integrated with clinicopathological information reveals novel and rare mutations in atypical, suspected and unknown cases of Alport syndrome or proteinuria PMID:24130771
• The American Journal of Pathology • 2008 • Sall1, sall2, and sall4 are required for neural tube closure in mice PMID:18818376
• PLoS One • 2013 • Wild type p53 transcriptionally represses the SALL2 transcription factor under genotoxic stress PMID:24040083
• Molecular Oncology • 2018 • SALL2 represses cyclins D1 and E1 expression and restrains G1/S cell cycle transition and cancer-related phenotypes PMID:29689621

Evidence Based Scoring (AI generated)