[O25] 一般口演 25　次世代シークエンス（NGS）解析

[O25-2] 次世代シークエンサーを用いたMonogenic diabetesのスクリーニング

^○岩崎 直子^1,2,3,4, 田中 慧^2,3, 赤川 浩之² (1.東京女子医科大学附属成人医学センター 糖尿病内科, 2.東京女子医科大学 総合医科学研究所, 3.東京女子医科大学 糖尿病代謝内科, 4.東京女子医科大学 ゲノム診療科)

Results of genetic screening for monogenic diabetes using whole exome sequencing (WES) were found in other countries, though such data has not been reported in Japan. Patients who were clinically diagnosed with MODY were consented for participation in this study. Seventy-two patients (M/F, 22/50), including 62 subjects who were negative for previous sanger sequencing or panel sequencing for MODY1, MODY2, MODY3 and MODY5 were analyzed. Genomic DNA samples were subjected to exome enrichment using a SureSelect Human All Exon V6 kit. Enriched DNA libraries were sequenced using a NovaSec6000 (Illumina Inc, San Diego, CA). Variants were annotated with 1000 genome, PolyPhen2, SIFT, CADD, ClinVar and gnomAD. Copy number variation (CNV) was evaluated by eXome Hidden Markov Model (XHMM) and confirmed by Multiplex Ligation dependent Probe Amplification (MLPA). Pathogenicity was evaluated according to ACMG guideline 2015. Among 10 subjects whose analyses was started by WES, pathogenic variants were found in seven subjects (three in HNF1A, two in HNF4A, one each in GCK and HNF1B).The detection rate was 70%. In the second group consisted with subjects who were negative for previous sanger sequencing and panel sequencing, we found pathogenic variant each in PDX1, ABCC8, INSR, and WFS1. In addition, a large genomic deletion was found in HNF4A in one subject by XHMM and confirmed by MLPA. Thus, the tentative detection rate was 8.1% (5/62) in the second group. Overall, 12/72(16.7%) clinically suspected MODY were found to have pathogenic variants in known monogenic diabetes genes.