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Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.
Iwama, Kazuhiro; Mizuguchi, Takeshi; Takeshita, Eri; Nakagawa, Eiji; Okazaki, Tetsuya; Nomura, Yoshiko; Iijima, Yoshitaka; Kajiura, Ichiro; Sugai, Kenji; Saito, Takashi; Sasaki, Masayuki; Yuge, Kotaro; Saikusa, Tomoko; Okamoto, Nobuhiko; Takahashi, Satoru; Amamoto, Masano; Tomita, Ichiro; Kumada, Satoko; Anzai, Yuki; Hoshino, Kyoko; Fattal-Valevski, Aviva; Shiroma, Naohide; Ohfu, Masaharu; Moroto, Masaharu; Tanda, Koichi; Nakagawa, Tomoko; Sakakibara, Takafumi; Nabatame, Shin; Matsuo, Muneaki; Yamamoto, Akiko; Yukishita, Shoko; Inoue, Ken; Waga, Chikako; Nakamura, Yoko; Watanabe, Shoko; Ohba, Chihiro; Sengoku, Toru; Fujita, Atsushi; Mitsuhashi, Satomi; Miyatake, Satoko; Takata, Atsushi; Miyake, Noriko; Ogata, Kazuhiro; Ito, Shuichi; Saitsu, Hirotomo; Matsuishi, Toyojiro; Goto, Yu-Ichi; Matsumoto, Naomichi.
Afiliação
  • Iwama K; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Mizuguchi T; Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Takeshita E; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Nakagawa E; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Okazaki T; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Nomura Y; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Iijima Y; Department of Pediatrics, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan.
  • Kajiura I; Yoshiko Nomura Neurological Clinic for Children, Tokyo, Japan.
  • Sugai K; Division of Pediatrics, Osaka Developmental Rehabilitation Center, Osaka, Japan.
  • Saito T; Division of Pediatrics, Osaka Developmental Rehabilitation Center, Osaka, Japan.
  • Sasaki M; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Yuge K; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Saikusa T; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Okamoto N; Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
  • Takahashi S; Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
  • Amamoto M; Deparment of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.
  • Tomita I; Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
  • Kumada S; Department of Pediatrics, Kitakyushu Municipal Yahata Hospital, Fukuoka, Japan.
  • Anzai Y; Department of Pediatrics, Kitakyushu Municipal Yahata Hospital, Fukuoka, Japan.
  • Hoshino K; Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
  • Fattal-Valevski A; Segawa Memorial Neurological Clinic for Children, Tokyo, Japan.
  • Shiroma N; Segawa Memorial Neurological Clinic for Children, Tokyo, Japan.
  • Ohfu M; Pediatric Neurology Unit, Dana-Dwek Children's Hospital, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Moroto M; Neurodevelopment Clinic Prop, Okinawa, Japan.
  • Tanda K; Division of Child Neurology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan.
  • Nakagawa T; Department of Pediatrics, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
  • Sakakibara T; Kyoto Prefectural Chutan-Nishi Public Health Center, Kyoto, Japan.
  • Nabatame S; Department of Pediatrics, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
  • Matsuo M; Department of Pediatrics, Nara Medical University, Nara, Japan.
  • Yamamoto A; Department of Pediatrics, Nara Medical University, Nara, Japan.
  • Yukishita S; Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Inoue K; Department of Pediatrics, Saga University, Faculty of Medicine, Saga, Japan.
  • Waga C; Division of Pediatrics, Tokyo Metropolitan Tobu Medical Center for Persons with Developmental and Multiple Disabilities, Tokyo, Japan.
  • Nakamura Y; Yoshiko Nomura Neurological Clinic for Children, Tokyo, Japan.
  • Watanabe S; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Ohba C; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Sengoku T; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Fujita A; Department of Genome Medicine Development, Medical Genome Center (MGC), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Mitsuhashi S; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Miyatake S; Department of Biochemistry, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Takata A; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Miyake N; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Ogata K; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Ito S; Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Japan.
  • Saitsu H; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Matsuishi T; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Goto YI; Department of Biochemistry, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Matsumoto N; Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
J Med Genet ; 56(6): 396-407, 2019 06.
Article em En | MEDLINE | ID: mdl-30842224
BACKGROUND: Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape of MECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES). METHODS: We performed WES on 77 MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria. RESULTS: Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including MECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H+ transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2). CONCLUSIONS: Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Variação Genética / Síndrome de Rett / Predisposição Genética para Doença / Estudos de Associação Genética / Sequenciamento do Exoma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenótipo / Variação Genética / Síndrome de Rett / Predisposição Genética para Doença / Estudos de Associação Genética / Sequenciamento do Exoma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article