Genomic backgrounds of Japanese patients with undiagnosed neurodevelopmental disorders
| Autor: | Tokito Yamaguchi, Keiko Yamamoto-Shimojima, Hirokazu Oguni, Ryutaro Kira, Ken Momosaki, Taichi Imaizumi, Akihiko Ishiyama, Pin Fee Chong, Shino Shimada, Hiroo Oomatsu, Katsumi Imai, Toshiyuki Seto, Hirokazu Kurahashi, Riyo Ueda, Eri Takeshita, Katsuhiro Kobayashi, Toshiyuki Yamamoto, Tomoe Yanagishita, Shiro Ozasa, Nobuhiko Okamoto, Tomoyuki Akiyama, Yongping Lu, Akihisa Okumura, Hikaru Kitahara |
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| Rok vydání: | 2019 |
| Předmět: |
Male
DNA Copy Number Variations Genetic counseling CDKL5 SYNGAP1 Bioinformatics Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Asian People Japan Developmental Neuroscience Intellectual disability medicine Humans Genetic Predisposition to Disease Exome X-linked recessive inheritance business.industry General Medicine medicine.disease Neurodevelopmental Disorders CHD2 Autism spectrum disorder Child Preschool Pediatrics Perinatology and Child Health Female Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Brain and Development. 41:776-782 |
| ISSN: | 0387-7604 |
| DOI: | 10.1016/j.braindev.2019.05.007 |
| Popis: | Background Recently, many genes related to neurodevelopmental disorders have been identified by high-throughput genomic analysis; however, a comprehensive understanding of the mechanism underlying neurodevelopmental disorders remains to be established. To further understand these underlying mechanisms, we performed a comprehensive genomic analysis of patients with undiagnosed neurodevelopmental disorders. Methods Genomic analysis using next-generation sequencing with a targeted panel was performed for a total of 133 Japanese patients (male/female, 81/52) with previously undiagnosed neurodevelopmental disorders, including developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy. Genomic copy numbers were also analyzed using the eXome Hidden Markov Model (XHMM). Results Thirty-nine patients (29.3%) exhibited pathogenic or likely pathogenic findings with single-gene variants or chromosomal aberrations. Among them, 20 patients were presented here. Pathogenic or likely pathogenic variants were identified in 18 genes, including ACTG1, CACNA1A, CHD2, CDKL5, DNMT3A, EHMT1, GABRB3, GABRG2, GRIN2B, KCNQ3, KDM5C, MED13L, SCN2A, SHANK3, SMARCA2, STXBP1, SYNGAP1, and TBL1XR1. Conclusion A diagnostic yield of 29.3% in this study was nearly the same as that previously reported from other countries. Thus, we suggest that there is no difference in genomic backgrounds in Japanese patients with undiagnosed neurodevelopmental disabilities. Although most of the patients possessed de novo variants, one of the patients showed an X-linked inheritance pattern. As X-linked recessive disorders exhibit the possibility of recurrent occurrence in the family, comprehensive molecular diagnosis is important for genetic counseling. |
| Databáze: | OpenAIRE |
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