مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Identification of a Novel Variant in the PODXL Gene in a Turkish Family With Focal Segmental Glomerulosclerosis
Identification of a Novel Variant in the PODXL Gene in a Turkish Family With Focal Segmental Glomerulosclerosis
Maryam Esmaeilzadeh Aghjeh,1,*Ilknur Suer,2Tugba Kalayci,3Ahmet Burak Dirim,4Murat Kaya,5Sukru Ozturk,6
1. Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 2. Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 3. Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 4. Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 5. Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 6. Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Introduction: Focal Segmental Glomerulosclerosis (FSGS) is a clinicopathological disorder characterized by podocyte injury, leading to defective glomerular filtration and severe proteinuria, often progressing to end-stage renal disease (ESRD). Advancements in recent genomics and genetics studies have demonstrated the major contribution of genetic alterations, especially in podocyte-associated proteins, in the pathogenesis of FSGS. In this study, we present the new variant in the PODXL gene that is related to FSGS. The PODXL gene is located on 7q32-q33 and contains 9 exons that encode podocalyxin, a protein that is highly expressed by podocytes.
Methods: Whole exome sequencing was conducted on a 47-year-old Turkish woman with biopsy-proven FSGS to identify the underlying molecular etiopathogenesis utilizing the Illumina NextSeq2000 system. Bioinformatic analyses were performed on the SOPHIA DDM platform. Sanger sequencing was conducted to validate the detected variant in the proband and to conduct segregation analysis in her family members.
Results: A novel heterozygous c.706+1G>A splice site variant of the PODXL gene was identified in the proband. This variant was confirmed in the proband by Sanger sequence analysis, and it was also detected in the other two affected family members but not in the healthy family member. This variant has not been previously reported in the ClinVar and HGMD databases. According to ACMG, it is classified as pathogenic variation (PVS1, PM2, PP3). Data obtained from in silico tools, the Franklin, and the Varsome databases suggest that the identified variant may have a pathogenic role in FSGS.
Conclusion: This case provides new information about the FSGS phenotype, highlighting the presence of a novel variant not previously described in the literature. Our findings establish the first instance of a splice donor +1 variant of the PODXL gene in a Turkish familial FSGS. Further functional studies to elucidate the mechanisms of action of this variant in FSGS could significantly contribute to determining the genetic etiology of FSGS and improving the accuracy of differential diagnosis.