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Abstract: SA-PO557

Immunohistochemistry Staining of Type-4 Collagen Does Not Predict the Expression of COL4A3/4/5 in a Genomic Variant of Focal Segmental Glomerulosclerosis

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Isaranuwatchai, Suramath, Chulalongkorn University, Bangkok, Thailand
  • Puapatanakul, Pongpratch, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Surintrspanont, Jerasit, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Iampenkhae, Kroonpong, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Makyoo, Jutamad, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Chaichana, Thiamjit, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Chanakul, Ankanee, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Kanjanabuch, Talerngsak, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Praditpornsilpa, Kearkiat, Chulalongkorn University, Bangkok, Bangkok, Thailand
Background

Focal segmental glomerulosclerosis (FSGS) is one of the kidney diseases with high rate of monogenic mutation. Variants in COL4A3, COL4A4, and COL4A5 genes were reported to be the most common cause of FSGS. We conducted an immunohistochemistry (IHC) staining of α3(IV) and α5(IV) collagen to see the correlation with the expression of COL4A3/4/5 and genetic variants of FSGS patients.

Methods

Whole-exome sequencing of FSGS patients were analyzed for COL4A3/4/5 variants and classified by American College of Medical Genetics guideline. Paraffin blocks of FSGS patients with variants in COL4A3/4/5 genes were recruited and went through IHC staining protocol. We used normal allograft kidney as positive control and confirmed Alport’s syndrome case as negative control.

Results

Eighteen FSGS patients with variants in COL4A3/4/5 genes were identified. One patient had a novel pathogenic variant (c.905delG, p.Gly302ValfsTer23) in COL4A4 gene. Another patient had a known likely pathogenic variant (c.2752G>A, p.Gly918Arg) in COL4A4 gene. Both of them had positive staining of α3(IV) and α5(IV) collagen, which means both patients express α3(IV) and α5(IV) collagen in their glomerular basement membrane (GBM), contradicting with our hypothesis that pathogenic variants should result in negative staining. Ten patients had variants of uncertain significance which six of them had positive staining and four of them had equivocal staining. Six patients had benign or likely benign variants in COL4A3/4/5 genes which four of them had positive staining and two of them had equivocal staining.

Conclusion

FSGS patients with COL4A3/4/5 genes variants all had α3(IV) and α5(IV) collagen expression in their GBM. The expression of α3(IV) and α5(IV) collagen by IHC staining was not correlated with COL4A3/4/5 genes variant classified by ACMG criteria.

Figure 1: Immunohistochemistry staining of α3(IV) and α5(IV) collagen

Funding

  • Government Support – Non-U.S.