Kosaki Kenjiro

写真a

Affiliation

School of Medicine, Center for Medical Genetics (Shinanomachi)

Position

Professor

E-mail Address

E-mail address

Related Websites

External Links

Profile Summary 【 Display / hide

  • clinical genetics multiple malformation syndrome genetic testing pediatrics

Academic Background 【 Display / hide

  • 1989.03

    Keio University, Faculty of Medicine

    University, Graduated

Licenses and Qualifications 【 Display / hide

  • 医師免許証, 1989.05

  • Japan Certified Board Pediatrician, 1993.07

  • American Board of Medical Genetics, 1996.06

  • 日本人類遺伝学会認定医, 1999.11

  • 日本人類遺伝学会・日本遺伝カウンセリング学会 臨床遺伝専門医制度 専門医指導医 , 2002.04

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Research Areas 【 Display / hide

  • Human genetics (multiple malformation syndromes)

 

Books 【 Display / hide

  • 遺伝子・染色体の異常と形態異常

    小崎健次郎, 2003

    Scope: 174-182

Papers 【 Display / hide

  • A Japanese girl with mild xeroderma pigmentosum group D neurological disease diagnosed using whole-exome sequencing

    Yokoi T., Enomoto Y., Uehara T., Kosaki K., Kurosawa K.

    Human Genome Variation (Human Genome Variation)  7 ( 1 )  2020.12

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    © 2020, The Author(s). We report a Japanese girl with mild xeroderma pigmentosum group D neurological disease. She had short stature, cataracts, intellectual disability, and mild skin symptoms. However, she was not clinically diagnosed. Using whole-exome sequencing, we identified compound heterozygous pathogenic variants in ERCC2. In the future, the patient may develop skin cancer and her neurological symptoms may progress. Early genetic testing is necessary to clarify the cause of symptoms in undiagnosed patients.

  • Novel ARX mutation identified in infantile spasm syndrome patient

    Takeshita Y., Ohto T., Enokizono T., Tanaka M., Suzuki H., Fukushima H., Uehara T., Takenouchi T., Kosaki K., Takada H.

    Human Genome Variation (Human Genome Variation)  7 ( 1 )  2020.12

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    © 2020, The Author(s). We report a 7-year-old boy with infantile spasms caused by a novel mutation in the Aristaless-related homeobox (ARX) gene. He showed infantile spasms and hypsarrhythmia on electroencephalogram from early infancy. Brain MRI did not reveal severe malformation of the brain except mild hypoplasia of the corpus callosum. Two-fold adrenocorticotropic hormone (ACTH) therapy failed to control the seizures, and ketogenic diet therapy and multi-antiepileptic drug therapy were required as he showed intractable daily tonic-clonic seizures. Exome sequencing identified a hemizygous mutation in the ARX gene, NG_008281.1(ARX_v001):c.1448 + 1 G > A, chrX: 25025227 C > T (GRCh37). To our knowledge, this mutation has not been reported previously.

  • Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency

    Yang L., Fujinami K., Ueno S., Kuniyoshi K., Hayashi T., Kondo M., Mizota A., Naoi N., Shinoda K., Kameya S., Fujinami-Yokokawa Y., Liu X., Arno G., Pontikos N., Kominami T., Terasaki H., Sakuramoto H., Katagiri S., Mizobuchi K., Nakamura N., Mawatari G., Kurihara T., Tsubota K., Miyake Y., Yoshitake K., Iwata T., Tsunoda K., Nishimura T., Hayashizaki Y., Shimozawa N., Horiguchi M., Yamamoto S., Kuze M., Machida S., Shimada Y., Nakamura M., Fujikado T., Hotta Y., Takahashi M., Mochizuki K., Murakami A., Kondo H., Ishida S., Nakazawa M., Hatase T., Matsunaga T., Maeda A., Noda K., Tanikawa A., Yamamoto S., Yamamoto H., Araie M., Aihara M., Nakazawa T., Sekiryu T., Kashiwagi K., Kosaki K., Piero C., Fukuchi T., Hayashi A., Hosono K., Mori K., Tanaka K., Furuya K., Suzuki K., Kohata R., Yanagi Y., Minegishi Y., Iejima D., Suga A., Rossmiller B.P., Pan Y., Oshima T., Nakayama M., Yamamoto M., Minematsu N., Mori D., Kijima Y., Kurata K., Yamada N., Itoh M., Kawaji H., Murakawa Y.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    © 2020, The Author(s). Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders.

  • De novo 2q36.3q37.1 deletion encompassing TRIP12 and NPPC yields distinct phenotypes

    Kondo Y., Aoyama K., Suzuki H., Hattori A., Hori I., Ito K., Yoshida A., Koroki M., Ueda K., Kosaki K., Saitoh S.

    Human Genome Variation (Human Genome Variation)  7 ( 1 )  2020.12

     View Summary

    © 2020, The Author(s). We report a patient with developmental delay, extremely short stature, small hands, dysmorphic facial features, hearing loss, and epilepsy carrying a de novo 2.76-Mb deletion of 2q36.3q37.1, including TRIP12 and NPPC. TRIP12 haploinsufficiency causes developmental delay with isolated dysmorphic facial features, whereas NPPC haploinsufficiency causes short stature and small hands. This is the first report of a unique phenotype, which is secondary to a microdeletion encompassing TRIP12 and NPPC.

  • Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association

    Fujinami-Yokokawa Y., Fujinami K., Kuniyoshi K., Hayashi T., Ueno S., Mizota A., Shinoda K., Arno G., Pontikos N., Yang L., Liu X., Sakuramoto H., Katagiri S., Mizobuchi K., Kominami T., Terasaki H., Nakamura N., Kameya S., Yoshitake K., Miyake Y., Kurihara T., Tsubota K., Miyata H., Iwata T., Tsunoda K., Nishimura T., Hayashizaki Y., Kondo M., Shimozawa N., Horiguchi M., Yamamoto S., Kuze M., Naoi N., Machida S., Shimada Y., Nakamura M., Fujikado T., Hotta Y., Takahashi M., Mochizuki K., Murakami A., Kondo H., Ishida S., Nakazawa M., Hatase T., Matsunaga T., Maeda A., Noda K., Tanikawa A., Yamamoto S., Yamamoto H., Araie M., Aihara M., Nakazawa T., Sekiryu T., Kashiwagi K., Kosaki K., Piero C., Fukuchi T., Hayashi A., Hosono K., Mori K., Tanaka K., Furuya K., Suzuki K., Kohata R., Yanagi Y., Minegishi Y., Iejima D., Suga A., Rossmiller B.P., Pan Y., Oshima T., Nakayama M., Teruyama Y., Yamamoto M., Minematsu N., Sanbe H., Mori D., Kijima Y., Mawatari G., Kurata K., Yamada N., Itoh M., Kawaji H., Murakawa Y.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

     View Summary

    © 2020, The Author(s). Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15–77/25–94). The median visual acuity in the right/left eye was 0.52/0.40 (range, −0.08–2.00/−0.18–1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

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Presentations 【 Display / hide

  • DHPLCを用いた稀少疾患に対する系統的遺伝子解析システムの開発: 多発奇形症候群を例として

    KOSAKI KENJIRO

    日本人類遺伝学会第50回大会 (倉敷) , 2005.09, Oral Presentation(general)

  • 日本人CHARGE連合患者の分子遺伝学的解析

    KOSAKI KENJIRO

    第108回日本小児科学会学術集会 (東京) , 2005.04, Public discourse, seminar, tutorial, course, lecture and others

  • 検査の外注における匿名化システム

    KOSAKI KENJIRO

    第2回全国遺伝子医療部門連絡会議 (京都) , 2004.12, Public discourse, seminar, tutorial, course, lecture and others

  • DHPLCを用いた系統的遺伝子解析システム

    KOSAKI KENJIRO

    第2回全国遺伝子医療部門連絡会議 (京都) , 2004.12, Oral Presentation(general)

  • 奇形症候群と遺伝子診断 最近のトピックス

    KOSAKI KENJIRO

    日本小児遺伝学会教育セミナー Dysmorphologyの夕べ第4回 (東京) , 2004.10, Public discourse, seminar, tutorial, course, lecture and others

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 先天異常遺伝子診断センターの確立

    2007.04
    -
    2008.03

    慶應義塾大学医学部坂口光洋記念慶應義塾医学振興基金慶應義塾大学医学研究奨励, Research grant

  • バイオインフォマティクスを用いたダイオキシン受容体標的遺伝子の系統的同定

    2003.04
    -
    2005.03

    Grant-in-Aid for Scientific Research, Research grant

  • 平成14〜16年度 厚生労働科学研究 効果的医療技術の確立推進臨床研究事業 「小児科診療における効果的薬剤使用のための遺伝子多型スクリーニングシステムの構築

    2002.04
    -
    2005.03

    Health and Labour Sciences Research Grants, Research grant

  • ヒューマンサイエンス振興財団「治験体制整備支援事業」

    2002.04
    -
    2003.03

    ヒューマンサイエンス振興財団, 治験体制整備支援事業, Research grant

  • 平成13〜14年度 文部科学省 科学研究費補助金  「先天異常とダイオキシン受容体関連蛋白の多型との相関:性腺機能障害と口蓋裂」

    2001.04
    -
    2002.03

    Grant-in-Aid for Scientific Research, Research grant

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Works 【 Display / hide

  • 学務委員会委員

    2003.10
    -
    2005.09

    Other

Intellectual Property Rights, etc. 【 Display / hide

  • 変異型DNAを検出するためのキット

    Application No.: 特願平11-357701  1999.12 

    Announcement No.: 特開2001-169781  2001.06 

    Patent, National application

Awards 【 Display / hide

  • 小児医学川野賞

    KOSAKI KENJIRO, 2009.03, 川野小児医学奨学財団, 小児消化器病学領域における遺伝子診断の臨床応用の促進

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • 三四会奨励賞

    Kosaki Kenjirou, 2000.11, 慶應義塾大学医学部三四会, ラッセルシルバー症候群に関する分子遺伝学的研究

  • 北島賞

    2018.08

    Type of Award: Keio commendation etc.

 

Courses Taught 【 Display / hide

  • MEDICAL PROFESSIONALISM 6

    2021

  • MEDICAL GENOMICS: SEMINAR

    2021

  • MEDICAL GENOMICS: PRACTICE

    2021

  • MCB(MOLECULAR CELL BIOLOGY)

    2021

  • LECTURE SERIES, PEDIATRICS

    2021

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Courses Previously Taught 【 Display / hide

  • pediatrics

    Keio University, 2017, Full academic year

  • Clinical genetics

    Keio University, 2017, Full academic year

Educational Activities and Special Notes 【 Display / hide

  • 慶應義塾大学医学部研究科委員会

    2011.07
    -
    Present

    , Special Affairs

 

Social Activities 【 Display / hide

  • 国立研究開発法人日本医療研究開発機構 東北メディカル・メガバンク計画プログラムオフィサー

    2017.04
    -
    2019.03
  • 国立研究開発法人日本医療研究開発機構課題評価委員

    2017.04
    -
    2019.03
  • Alliance for Translation of Genome science into Clinical medicine

    2006.11
    -
    Present

Memberships in Academic Societies 【 Display / hide

  • The Japan Society of Humana Genetics, 

    2002
    -
    Present
  • The Japan Society of Pediatric Genetics, 

    2012.04
    -
    Present
  • 日本先天異常学会, 

    2004
    -
    Present
  • 日本小児科学会, 

    1989.05
    -
    Present

Committee Experiences 【 Display / hide

  • 2002
    -
    2019.09

    Board of Councillors, The Japan Society of Human Genetics

  • 2019.11
    -
    2021.11

    理事長, 日本人類遺伝学会

  • 2019.07
    -
    2021.07

    理事長, 日本先天異常学会

  • 2017.07
    -
    2019.03

    専門委員, 独立行政法人医療品医療機器総合機構

  • 2017.04
    -
    2021.03

    学会評議員, 日本遺伝カウンセリング学会

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