Comparison between conventional and comprehensive sequencing approaches for genetic diagnosis of Alport syndrome.
Adult
Chloride Channels
/ genetics
Collagen
/ genetics
Female
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Laminin
/ genetics
Male
Membrane Proteins
/ genetics
Nephritis, Hereditary
/ diagnosis
Nuclear Proteins
/ genetics
Protein Tyrosine Phosphatases
/ genetics
Sequence Analysis, DNA
Alport syndrome
next-generation sequencing
podocyte-related gene
targeted exome sequencing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
11
12
2018
revised:
05
06
2019
accepted:
05
07
2019
pubmed:
1
8
2019
medline:
18
6
2020
entrez:
1
8
2019
Statut:
ppublish
Résumé
Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3-5 genes. Recently, comprehensive genetic analysis has become the first-line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published. In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next-generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group). In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%. Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathogenic mutations missed by Sanger sequencing.
Sections du résumé
BACKGROUND
Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3-5 genes. Recently, comprehensive genetic analysis has become the first-line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published.
METHODS
In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next-generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group).
RESULTS
In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%.
DISCUSSION
Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathogenic mutations missed by Sanger sequencing.
Identifiants
pubmed: 31364286
doi: 10.1002/mgg3.883
pmc: PMC6732293
doi:
Substances chimiques
CLC-5 chloride channel
0
Chloride Channels
0
Intracellular Signaling Peptides and Proteins
0
Laminin
0
Membrane Proteins
0
Nuclear Proteins
0
nephrin
0
laminin beta2
124148-86-3
Collagen
9007-34-5
EYA1 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatases
EC 3.1.3.48
Types de publication
Clinical Trial
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e883Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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