| Autor: |
Kazuhiro Iwama, Takeshi Mizuguchi, Eri Takeshita, Eiji Nakagawa, Tetsuya Okazaki, Yoshiko Nomura, Yoshitaka Iijima, Ichiro Kajiura, Kenji Sugai, Takashi Saito, Masayuki Sasaki, Kotaro Yuge, Tomoko Saikusa, Nobuhiko Okamoto, Satoru Takahashi, Masano Amamoto, Ichiro Tomita, Satoko Kumada, Yuki Anzai, Kyoko Hoshino |
| Zdroj: |
Journal of Medical Genetics; Jun2019, Vol. 56 Issue 6, p396-407, 12p |
| Abstrakt: |
Background R ett 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 singlenucleotide 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 AT Pase H+ transporting V0 subunit A1 (ATP6V0A1), ubiquitinspecific 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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