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Next-generation sequencing in patients with familial FSGS: first report of collagen gene mutations in Tunisian patients

Journal of Human Genetics volume 66, pages 795–803 (2021)Cite this article

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Abstract

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. FSGS is considered as a podocyte disease due to the fact that in the majority of patients with FSGS, the lesion results from defects in the podocyte structure. However, FSGS does not result exclusively from podocyte-associated genes. In this study, we used a genetic approach based on targeted next-generation sequencing (NGS) of 242 genes to identify the genetic cause of FSGS in seven Tunisian families. The sequencing results revealed the presence of eight distinct mutations including seven newly discovered ones: the c.538G>A (p.V180M) in NPHS2, c.5186G>A (p.R1729Q) in PLCE1 and c.232A>C (p.I78L) in PAX2 and five novel mutations in COL4A3 and COL4A4 genes. Four mutations (c.209G>A (p.G70D), c.725G>A (p.G242E), c.2225G>A (p.G742E), and c. 1681_1698del) were detected in COL4A3 gene and one mutation (c.1424G>A (p.G475D)) was found in COL4A4. In summary, NGS of a targeted gene panel is an ideal approach for the genetic testing of FSGS with multiple possible underlying etiologies. We have demonstrated that not only podocyte genes but also COL4A3/4 mutations should be considered in patients with FSGS.

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Acknowledgements

We are indebted to the patients and their families for their invaluable cooperation and for providing the blood samples. This research was funded by the Tunisian Ministry of Higher Education and Scientific Research.

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Authors and Affiliations

  1. Renal pathology research laboratory LR19ES11, Department of Nephrology, Hedi Chaker University Hospital, Sfax, Tunisia

    Sawssan Ammar, Houda Kanoun, Khawla Kammoun, Mohamed Ben Hmida & Faiçal Jarraya

  2. Human Genetic Laboratory, University Hospital Hedi Chaker, Sfax, Tunisia

    Houda Kanoun & Hassen Kamoun

  3. Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Cartagena 340-350, 08025, Barcelona, Catalonia, Spain

    Andrea Domingo-Gallego, Patricia Ruiz, Laura Lorente-Grandoso, Marc Pybus & Elisabet Ars

  4. Department of Pediatry, University Hospital Hedi Chaker, Sfax, Tunisia

    Bayen Maalej

  5. Department of Pathology, Habib Bourguiba University Hospital, Sfax, Tunisia

    Tahya Boudawara

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  1. Sawssan Ammar
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Correspondence to Sawssan Ammar.

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Ammar, S., Kanoun, H., Kammoun, K. et al. Next-generation sequencing in patients with familial FSGS: first report of collagen gene mutations in Tunisian patients. J Hum Genet 66, 795–803 (2021). https://doi.org/10.1038/s10038-021-00912-2

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