Next-generation sequencing in patients with familial FSGS: first report of collagen gene mutations in Tunisian patients.
Adult
Autoantigens
/ genetics
Collagen
/ genetics
Collagen Type IV
/ genetics
Female
Genetic Diseases, Inborn
/ diagnosis
Genetic Predisposition to Disease
Genetic Testing
/ methods
Glomerulosclerosis, Focal Segmental
/ diagnosis
High-Throughput Nucleotide Sequencing
/ methods
Humans
Male
Mutation, Missense
PAX2 Transcription Factor
/ genetics
Pedigree
Podocytes
/ physiology
Tunisia
Young Adult
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
20
11
2020
accepted:
16
02
2021
revised:
09
01
2021
pubmed:
4
3
2021
medline:
15
12
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33654185
doi: 10.1038/s10038-021-00912-2
pii: 10.1038/s10038-021-00912-2
doi:
Substances chimiques
Autoantigens
0
COL4A4 protein, human
0
Collagen Type IV
0
PAX2 Transcription Factor
0
PAX2 protein, human
0
type IV collagen alpha3 chain
0
Collagen
9007-34-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
795-803Informations de copyright
© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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