Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi
{"title":"与自闭症谱系障碍相关的 CHD8、KMT2C、EP300 和 TCF4 基因变异病例报告","authors":"Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi","doi":"10.1016/j.genrep.2024.102074","DOIUrl":null,"url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in <em>CHD8</em> (benign), <em>KMT2C</em> (likely pathogenic), and <em>EP300 and TCF4</em> (uncertain significance). Despite the benign classification of the <em>CHD8</em> variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic <em>KMT2C</em> frameshift mutation and deletions in <em>EP300 and TCF4</em> suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A case report on genetic variants in CHD8, KMT2C, EP300, and TCF4 associated with autism spectrum disorder\",\"authors\":\"Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi\",\"doi\":\"10.1016/j.genrep.2024.102074\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in <em>CHD8</em> (benign), <em>KMT2C</em> (likely pathogenic), and <em>EP300 and TCF4</em> (uncertain significance). Despite the benign classification of the <em>CHD8</em> variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic <em>KMT2C</em> frameshift mutation and deletions in <em>EP300 and TCF4</em> suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.</div></div>\",\"PeriodicalId\":12673,\"journal\":{\"name\":\"Gene Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gene Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2452014424001973\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014424001973","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
A case report on genetic variants in CHD8, KMT2C, EP300, and TCF4 associated with autism spectrum disorder
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in CHD8 (benign), KMT2C (likely pathogenic), and EP300 and TCF4 (uncertain significance). Despite the benign classification of the CHD8 variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic KMT2C frameshift mutation and deletions in EP300 and TCF4 suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.
Gene ReportsBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍:
Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.