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

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 wit...

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Bibliographic Details
Published in:	Journal of human genetics Vol. 66; no. 8; pp. 795 - 803
Main Authors:	Ammar, Sawssan, Kanoun, Houda, Kammoun, Khawla, Domingo-Gallego, Andrea, Ruiz, Patricia, Lorente-Grandoso, Laura, Pybus, Marc, Maalej, Bayen, Boudawara, Tahya, Kamoun, Hassen, Ben Hmida, Mohamed, Ars, Elisabet, Jarraya, Faiçal
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01-08-2021
Subjects:	Collagen Collagen (type IV) Genes Genetic screening Mutation Next-generation sequencing Patients Pax2 protein Proteinuria
Online Access:	Get full text
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1434-5161 1435-232X
DOI:	10.1038/s10038-021-00912-2