講演情報
[O27-2]レトロトランスポジション挿入によるEBP遺伝子破断により発症したX連鎖優性点状軟骨異形成症(CDPX2)の母子例
○平出 拓也1,2, 増永 陽平1, 本多 彰3, 加藤 芙弥子4, 福田 冬季子1,4, 深見 真紀5, 中島 光子2, 才津 浩智2, 緒方 勤1,2,6 (1.浜松医科大学 小児科, 2.浜松医科大学 医化学講座, 3.東京医科大学茨城医療センター 共同研究センター, 4.浜松医科大学 浜松成育医療学講座, 5.国立成育医療研究センター研究所 分子内分泌研究部, 6.浜松医療センター 小児科)
X-linked dominant chondrodysplasia punctata (CDPX2) is a rare congenital disorder caused by pathogenic variants in EBP on Xp11.23. We encountered a girl and her mother with CDPX2-compatible phenotypes including punctiform calcification in the neonatal period of the girl, and asymmetric limb shortening and ichthyosis following the Blaschko lines in both subjects. Serum sterol profile analysis indicated impaired 3β-hydroxysteroid Δ8,Δ7-sterol isomerase activity. Although Sanger direct sequencing failed to reveal a disease-causing variant in EBP, genome sequencing followed by Manta analysis identified a ~ 4.5 kb insertion at EBP exon 2 of both subjects. The inserted sequence contained the hallmarks of retrotransposition such as an antisense poly(A) tail, target site duplication and consensus endonuclease cleavage site, and harbored SVA_F1 element with 5’- and 3’-transductions containing the Alu sequence. Since the inserted sequence showed high homology with 10q24.2 and 19q12 loci, it is likely that the 19p12 sequence, which was generated by the insertion of 10q24.2 sequence followed by truncation during the evolution, was inserted into EBP of the mother by retrotransposition. The results imply the relevance of retrotransposition to the human genetic diseases and the usefulness of genome sequencing in the identification of retrotransposition.