論文 - 詳細
| RRC ID | 55007 |
|---|---|
| 著者 | Fan Y, Yin W, Hu B, Kline AD, Zhang VW, Liang D, Sun Y, Wang L, Tang S, Powis Z, Li L, Yan H, Shi Z, Yang X, Chen Y, Wang J, Jiang Y, Tan H, Gu X, Wu L, Yu Y. |
| タイトル | De Novo Mutations of CCNK Cause a Syndromic Neurodevelopmental Disorder with Distinctive Facial Dysmorphism. |
| ジャーナル | Am J Hum Genet |
| Abstract |
Neurodevelopment is a transcriptionally orchestrated process. Cyclin K, a regulator of transcription encoded by CCNK, is thought to play a critical role in the RNA polymerase II-mediated activities. However, dysfunction of CCNK has not been linked to genetic disorders. In this study, we identified three unrelated individuals harboring de novo heterozygous copy number loss of CCNK in an overlapping 14q32.3 region and one individual harboring a de novo nonsynonymous variant c.331A>G (p.Lys111Glu) in CCNK. These four individuals, though from different ethnic backgrounds, shared a common phenotype of developmental delay and intellectual disability (DD/ID), language defects, and distinctive facial dysmorphism including high hairline, hypertelorism, thin eyebrows, dysmorphic ears, broad nasal bridge and tip, and narrow jaw. Functional assay in zebrafish larvae showed that Ccnk knockdown resulted in defective brain development, small eyes, and curly spinal cord. These defects were partially rescued by wild-type mRNA coding CCNK but not the mRNA with the identified likely pathogenic variant c.331A>G, supporting a causal role of CCNK variants in neurodevelopmental disorders. Taken together, we reported a syndromic neurodevelopmental disorder with DD/ID and facial characteristics caused by CCNK variations, possibly through a mechanism of haploinsufficiency. |
| 巻・号 | 103(3) |
| ページ | 448-455 |
| 公開日 | 2018-9-6 |
| DOI | 10.1016/j.ajhg.2018.07.019 |
| PII | S0002-9297(18)30246-5 |
| PMID | 30122539 |
| PMC | PMC6128244 |
| MeSH | Abnormalities, Multiple / genetics* Adolescent Animals Child Child, Preschool Craniofacial Abnormalities / genetics* Cyclins / genetics* Developmental Disabilities / genetics* Female Haploinsufficiency / genetics Heterozygote Humans Hypertelorism / genetics Intellectual Disability / genetics Male Muscular Atrophy / genetics* Musculoskeletal Abnormalities / genetics Mutation / genetics* Nervous System Malformations / genetics Neurodevelopmental Disorders / genetics* Phenotype Syndrome Zebrafish |
| IF | 9.924 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tol-056 |