Comparison between conventional and comprehensive sequencing approaches for genetic diagnosis of Alport syndrome

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 forCOL4A3/COL4A4/COL4A5 (n = 294, Sanger group).ResultsIn the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes,NPHS1 andEYA1. 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 inCLCN5 orLAMB2. The final variant detection rate was 90%.DiscussionOur 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.

Source: Molecular Genetics & Genomic Medicine - July 29, 2019 Category: Genetics & Stem Cells Authors: Tomohiko Yamamura, Kandai Nozu, Shogo Minamikawa, Tomoko Horinouchi, Nana Sakakibara, China Nagano, Yuya Aoto, Shinya Ishiko, Koichi Nakanishi, Yuko Shima, Hiroaki Nagase, Rini Rossanti, Ming J. Ye, Yoshimi Nozu, Shingo Ishimori, Naoya Mori Tags: ORIGINAL ARTICLE Source Type: research