Academic Journal
Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing
| العنوان: | Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing |
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| المؤلفون: | 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 |
| بيانات النشر: | BMJ Publishing Group Ltd |
| سنة النشر: | 2019 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Diagnostics |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://jmg.bmj.com/cgi/content/short/56/6/396; http://dx.doi.org/10.1136/jmedgenet-2018-105775 |
| DOI: | 10.1136/jmedgenet-2018-105775 |
| الاتاحة: | http://jmg.bmj.com/cgi/content/short/56/6/396 https://doi.org/10.1136/jmedgenet-2018-105775 |
| Rights: | Copyright (C) 2019, BMJ Publishing Group Ltd |
| رقم الانضمام: | edsbas.1735DE6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/jmedgenet-2018-105775 |
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