講演情報
[P23-1]全ゲノムシーケンスとFISH解析により腕内逆位関連病的変異が同定されたメープルシロップ尿症の一例
○横井 克幸1,2, 中島 葉子1, 須藤 湧太1, 真里谷 奨3, 河村 理恵2, 堤 真紀子2, 稲垣 秀人2, 吉川 哲史1, 伊藤 哲哉1, 倉橋 浩樹2 (1.藤田医科大学 医学部 小児科, 2.藤田医科大学 総合医科学研究所 分子遺伝学分野, 3.札幌医科大学 医学部 産婦人科学講座)
Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched-chain amino acid metabolism caused by mutations in BCKDHA, BCKDHB, and DBT that encode the E1α, E1β, and E2 subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Various MSUD-causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the first classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA: a missense variant (NM_000709.3:c.757G＞A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting intron 1 of BCKDHA, which was identified by whole-genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction-specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal/preimplantation tests are necessary.