当科の紹介

外木秀文（非常勤）　天使病院小児科　　小児科専門医、臨床遺伝指導医

1.染色体異常症の診断・遺伝学的検査・遺伝相談
2.染色体異常症患児の定期検診・療育相談
3.先天奇形症候群・種々の先天異常の診断、診療、遺伝相談

天使病院・北海道医療大学などと共同で先天奇形症候群の遺伝子異常・治療法の研究を、特にベックウィズ・ウィードマン症候群、プラダー・ウィリー症候群，シルバー・ラッセル症候群，ウィリアムズ症候群，歌舞伎症候群，ダウン症候群，ヌーナン症候群などの方々を対象に行っている。今後、原因不明の遺伝性疾患について，IRUDプロジェクトにも積極的にかかわっていきたいと思っています。

1. Dai, J., Kim, O.-H., Cho, T.-J., Schmidt-Rimpler, M., Tonoki, H., Takikawa, K., Haga, N., Miyoshi, K., Kitoh, H., Yoo, W.-J., Choi, I.-H., Song, H.-R., and 23 others (2010) Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. J. Med. Genet. 47: 704-709,.

2. Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki, H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ.(2011) Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am J Med Genet A.155:1511-1516.

3. Tonoki, H, Harada N, Shimokawa O, Yosozumi A, Monzaki K, Satoh K, Kosaki R, Sato A, Matsumoto N, Iizuka S (2011) Axenfeld-Rieger Anomaly and Axenfeld-Rieger Syndrome; Clinical and Molecular-Cytogenetic and DNA Array Analyses on Three Patients with Chromosomal Defects at 6p25. Am J Med Genet A, 151: 2925-2932.

4. Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, Mabe H, Watanabe Y, Yoshino M, Matsuishi T, Takanashi JI, Shotelersuk V, Tekin M, Ochi N, Kubota M, Ito N, Ihara K, Hara T, Tonoki, H, Ohta T, Saito K, Matsuo M, Urano M, Enokizono T, Sato A, Tanaka H, Ogawa A, Fujita T, Hiraki Y, Kitanaka S, Matsubara Y, Makita T, Taguri M, Nakashima M, Tsurusaki Y, Saitsu H, Yoshiura KI, Matsumoto N, Niikawa N.(2013) MLL2 and KDM6A mutations in patients with Kabuki syndrome. Am J Med Genet A. 161:2234-2243

5. Yamamoto S, Okuhara K, Tonoki, H, Iizuka S, Nihei N, Tajima T. (2013) A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome. Clin Pediatr Endocrinol. 22:83-86.

6. Maeda T, Higashimoto K, Jozaki K, Yatsuki H, Nakabayashi K, Makita Y, Tonoki, H, Okamoto N, Takada F, Ohashi H, Migita M, Kosaki R, Matsubara K, Ogata T, Matsuo M, Hamasaki Y, Ohtsuka Y, Nishioka K, Joh K, Mukai T, Hata K, Soejima H.　(2014) Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions to aberrant methylation in Beckwith-Wiedemann syndrome with epimutations. Genet Med 16:903-12.

7. Kaname T, Ki CS, Niikawa N, Baillie GS, Day JP, Yamamura KI, Ohta T, Nishimura G, Mastuura N, Kim OH, Sohn YB, Kim HW, Cho SY, Ko AR, Lee JY, Kim HW, Ryu SH, Rhee H, Yang KS, Joo K, Lee J, Kim CH, Cho KH, Kim D, Yanagi K, Naritomi K, Yoshiura KI, Kondoh T, Nii E, Tonoki, H, Houslay MD, Jin DK. (2014) Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis. Cell Signal 26:2446-59

8. Kishimoto K, Kobayashi R, Yonemaru N, Yamamoto H, Tsujioka T, Sano H, Suzuki D, Yasuda K, Suzuki M, Ando A, Tonoki, H, Iizuka S, Uetake K, Kobayashi K.　(2015) Refractory Sacrococcygeal Germ Cell Tumor in Schinzel-Giedion Syndrome. J Pediatr Hematol Oncol. 37:238-241.

9. Nagata E, Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki, H, Mizuno S, Watanabe S, Yoshiura K, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura G, Toda T, Takada S, Yokoyama S, Asahara H, Sano S, Fukami M, Ikegawa S, OgataT (2014)　Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. Orphanet Journal of Rare Diseases 2014, 9:125 http://www.ojrd.com/content/9/1/125 Orphanet J Rare Dis. 2014 Oct 21;9:125. doi: 10.1186/s13023-014-0125-5.

10. Mishima T, Watari M, Iwaki Y, Nagai T, Kawamata-Nakamura M, Kobayashi Y, Fujieda S, Oikawa M, Takahashi N, Keira M, Yoshida H, Tonoki, H. (2017) Miller-Dieker Syndrome with unbalanced translocation 45, X, psu dic(17;Y)(p13;p11.32) detected by Fluorescence in situ hybridization and G-banding analysis using high resolution banding technique. Congenit Anom (Kyoto) 57:61-63 2016 Sep 20. doi: 10.1111/cga.12193. [Epub ahead of print]

11. Hishimura N, Watari M, Ohata H, Fuseya N, Wakiguchi S, Tokutomi T, Okuhara K, Takahashi N, Iizuka S, Yamamoto H, Mishima T, Fujieda S, Kobayashi R, Cho K, Kuroda Y, Kurosawa K, Tonoki, H. (2016) Genetic and prenatal findings in two Japanese patients with Schinzel-Giedion syndrome.　Clin Case Rep. 2016 Nov 17;5(1):5-8. doi: 10.1002/ccr3.738. PMID:28096980

12. Hishimura-Yonemaru N, Okuhara K, Takahashi N, Tonoki, H, Iizuka S, Tajima T.　(2017)　
A case of 45,X/47,XXX mosaic Turner syndrome with limb length discrepancy.　Clin Pediatr Endocrinol. 2017;26(4):259-263.

13. Tsutsumi M, Fujita N, Suzuki F, Mishima T, Fujieda S, Watari M, Takahashi N, Tonoki, H, Moriwaka O, Endo T, Kurahashi H. (2018) A constitutional jumping translocation involving the Y and acrocentric chromosomes. Asian J Androl. 2018 Aug 17. doi:
10.4103/aja.aja_60_18. [Epub ahead of print] 2019 Asian J Androl .21: 101-103.

14. Tonoki, H. (2018) A brief history of genomic diagnosis: from chromosome to DNA array. Clin Pediatr 1:1002.

15. Yamoto K, Saitsu H, Nishimura G, Kosaki R, Takayama S, Haga N, Tonoki, H, Okumura A, Horii E, Okamoto N, Suzumura H, Ikegawa S, Kato F, Fujisawa Y, Nagata E, Takada S, Fukami M, Ogata T.　(2019)　Comprehensive clinical and molecular studies in split-hand/foot malformation: identification of two plausible candidate genes (LRP6 and UBA2).Eur J Hum Genet. 2019 Jul 22. doi: 10.1038/s41431-019-0473-7. [Epub ahead of print]

16. Hamada S, Kato C, Takahashi T, Hayashi A, Ueda Y, Sato Y, Tonoki, H, Okamoto T.　(2020) A girl presenting with gradually elevated levels of serum creatinine: Answers. Pediatr Nephrol. Jan 20. doi: 10.1007/s00467-020-04479-6. [Epub ahead of print]

17. Hamada S, Kato C, Takahashi T, Hayashi A, Ueda Y, Sato Y, Tonoki, H, Okamoto T.　(2020) A girl presenting with gradually elevated levels of serum creatinine: Questions. Pediatr Nephrol. Jan 20. doi: 10. 1007/s00467-020-04478-7. [Epub ahead of print]

18. Higashimoto K, Watanabe H, Tanoue Y, Tonoki, H, Tokutomi T, Hara S, Yatsuki H, Soejima H. (2021) Hypomethylation of a centromeric block of ICR1 is sufficient to cause Silver-Russell Syndrome. J Med Genet 58:422-425. doi:10.1136/jmedgenet-2020-106907

19. MaruoY, Egawa K, Tonoki, H, Terae S, Ueda Y, Shiraishi H (2021) Selective eating in autism spectrum disorder leading to kwashiorkor and brain edema. Pediatr Neurol 116:55-56

20. Yamada M, Suzuki H, Miya F, Kosugiyama K, Ujiie T, Tonoki, H, Kosaki K. (2023) Precise definition of the breakpoints of an apparently balanced translocation between chromosome 3q26 and chromosome 7q36: Role of KMT2C disruption. Congenit Anom (Kyoto). 2023 Mar 22. doi: 10.1111/cga.12514. Online ahead of print.PMID: 36946065

21. 外木秀文（2011）成人期のPrader-Willi症候群　Prader-Willi症候群　永井敏郎編　医学書院

22. 外木秀文 (2014)　染色体異常　こどもケア vol. 9 37-41

23. 外木秀文　(2015)　ベックウィズ・ウィーデマン症候群　今日の小児治療指針第16版　医学書院

24. 外木秀文 (2019) ダウン症候群の医療管理．成人期の自然歴―アンケートの結果をもとに　小児内科 51:865-870.

25. 白石春生，森岡圭太，高橋伸浩，松澤まき，澤井彩織，高桑千佳，脇口定衛，奥原宏治，三島隆，計良光昭，湊雅司，大場豪，山本浩史，藤山怜史，門崎圭美，外木秀文 (2019) 当院NICUで診療したダウン症候群の合併症の臨床的検討 臨床小児医学 67:21-26

26. 高橋伸浩，外木秀文　(2020) NICU卒業生の予後と診療のポイント　21 トリソミー．小児科診療　83:1171-1175.

27. 竹内千仙，玉井浩，植田紀美子，大橋博文，小野正恵，川目裕，北畠康司，小松知子，外木秀文，沼部博直，松尾真理　(2020) ダウン症のある患者の移行医療支援ガイド　日本ダウン症学会　ダウン症候群の移行診療に関わるタスクフォース

28. 外木秀文　(2020) ダウン症候群．今日の小児治療指針第17版　医学書院

29. 外木秀文　(2021)　ダウン症候群の移行支援ガイド　札医通信 648:14-16

30. 外木秀文 (2022) 先天異常　病気が見えるVol 15 小児科　pp156-173　メディックメディア　東京

31. ダウン症成人診療ガイドライン翻訳プロジェクト　竹内千仙，井手友美，植田紀美子，大石智，北畠康司，黒柳裕一，小松知子，玉井浩，外木秀文，橋本洋之　(2022) 日本語　版成人期ダウン症診療ガイドライン　Web公開　日本ダウン症学会