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論文
- タイトル
- タイトル（英）
- Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.
- 参照URL
- https://researchmap.jp/Yoshiaki_Kikkawa/published_papers/50031214
- 著者
- 著者（英）
- Hideki Mutai,Fuyuki Miya,Kiyomitsu Nara,Nobuko Yamamoto,Satomi Inoue,Haruka Murakami,Kazunori Namba,Hiroshi Shitara,Shujiro Minami,Atsuko Nakano,Yukiko Arimoto,Noriko Morimoto,Taiji Kawasaki,Koichiro Wasano,Masato Fujioka,Yasue Uchida,Kimitaka Kaga,Kazuki Yamazawa,Yoshiaki Kikkawa,Kenjiro Kosaki,Tatsuhiko Tsunoda,Tatsuo Matsunaga
- 担当区分
- 概要
- 概要（英）
- There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features. Causative genes were identified in 22 families, including both established genes associated with syndromic hearing loss (PTPN11, CHD7, KARS1, OPA1, DLX5, MITF, SOX10, MYO7A, and USH2A) and those associated with nonsyndromic hearing loss (STRC, EYA4, and KCNQ4). Association of a DLX5 variant with incomplete partition type I (IP-I) anomaly of the inner ear was identified in a patient with cleft lip and palate and acetabular dysplasia. The study identified COL1A1, CFAP52, and NSD1 as causative genes through phenotype similarity search or by analogy. ZBTB10 was proposed as a novel candidate gene for syndromic hearing loss with IP-I. A mouse model with homozygous Zbtb10 frameshift variant resulted in embryonic lethality, suggesting the importance of this gene for early embryonic development. Our data highlight a wide spectrum of rare causative genes in patients with syndromic hearing loss, and demonstrate that WES analysis combined with phenotype similarity search is a valuable approach for clinical genetic testing of undiagnosed disease.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Human genetics
- 巻
- 144
- 号
- 1
- 開始ページ
- 93
- 終了ページ
- 112
- 出版年月
- 2025年1月
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1007/s00439-024-02719-5
- 共同研究・競争的資金等の研究課題
研究者
吉川 欣亮
(キッカワ ヨシアキ)