講演情報
[OE2-1]全ゲノム長鎖型シーケンサーによるデノボ均衡型相互転座の切断点解析
○山田 茉未子1, 鈴木 寿人1, 外木 秀文2, 小杉山 清隆3, 氏家 武4, 宮 冬樹1, 武内 俊樹5, 小崎 健次郎1 (1.慶應義塾大学 医学部 臨床遺伝学センター, 2.天使病院臨床遺伝センター, 3.北海道大学病院小児科, 4.氏家記念こどもクリニック, 5.慶應義塾大学医学部小児科学教室)
Purpose: Analysis of breakpoints in patients with balanced reciprocal translocations with congenital anomalies has been a challenging task. Methods: Patients with balanced translocation of de novo mutations by G-banding were included in the study. Whole genome analysis was performed by nanopore long-read sequencer. Chromosome reconstructions near the breakpoints were analyzed and the breakpoints were determined at the base level. Patient 1 (46,XY,t(4:18)(q31;q11.2)dn): 4-year-old boy with intellectual disability, atrial septal defect, cleft lip and palate, micrognathia, and syndactyly. Patient 2 (46,XY,t(3:7)(q26.2;q36.1)dn): A 3-year-old boy with developmental delay and autism. Results: Patient 1: Array CGH revealed a 7 Mb deletion of Chr2. The deletion included the HOXD gene cluster for syndactyly and DLX1 and DLX2, for cleft lip and palate. There was only one breakpoint on derived Chr4, while derived Chr18 contained multiple rearrangement points. One of the rearrangement points was located within the first intron of TLL1 (Chr4:166797437), which is known to present atrial septal defects. Patient 2: Array CGH revealed a 6 Mb deletion of Chr 11. The breakpoints of the balanced translocation t(3:7) (q26.2;q36.1) was in the 3' UTR region of the SLC7A14 gene on Chr3:170183554 and in intron 43 of KMT2C gene on Chr7:151857653. Discussion: The complex post-rearrangement genome sequences resulting from the translocation were revealed, and a variety of symptoms were explained, and the cause of the disease was elucidated by the whole-genome long-read analysis.