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Pàgina inicial > Articles > Articles publicats > A Novel Intragenic Duplication in the HDAC8 Gene Underlying a Case of Cornelia de Lange Syndrome |
Data: | 2022 |
Resum: | Cornelia de Lange syndrome (CdLS) is a multisystemic genetic disorder characterized by distinctive facial features, growth retardation, and intellectual disability, as well as various systemic conditions. It is caused by genetic variants in genes related to the cohesin complex. Single-nucleotide variations are the best-known genetic cause of CdLS; however, copy number variants (CNVs) clearly underlie a substantial proportion of cases of the syndrome. The NIPBL gene was thought to be the locus within which clinically relevant CNVs contributed to CdLS. However, in the last few years, pathogenic CNVs have been identified in other genes such as HDAC8, RAD21, and SMC1A. Here, we studied an affected girl presenting with a classic CdLS phenotype heterozygous for a de novo ~32 kbp intragenic duplication affecting exon 10 of HDAC8. Molecular analyses revealed an alteration in the physiological splicing that included a 96 bp insertion between exons 9 and 10 of the main transcript of HDAC8. The aberrant transcript was predicted to generate a truncated protein whose accessibility to the active center was restricted, showing reduced ease of substrate entry into the mutated enzyme. Lastly, we conclude that the duplication is responsible for the patient's phenotype, highlighting the contribution of CNVs as a molecular cause underlying CdLS. |
Ajuts: | Instituto de Salud Carlos III PI19/01860 Instituto de Salud Carlos III DTS20-00024 Instituto de Salud Carlos III FIS PI20/01767 Instituto de Salud Carlos III FIS PI18/000687 Agencia Estatal de Investigación RTI2018-094434-B-I00 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Cornelia de Lange syndrome ; Genetic disorder ; Copy number variants ; HDAC8 ; Intragenic duplication ; Array CGH ; Genetic diagnosis |
Publicat a: | Genes, Vol. 13 Núm. 8 (august 2022) , p. 1413, ISSN 2073-4425 |
11 p, 1.4 MB |