Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals
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| Názov: | Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals |
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| Autori: | Dana E. Layo-Carris, Emily E. Lubin, Annabel K. Sangree, Kelly J. Clark, Emily L. Durham, Elizabeth M. Gonzalez, Sarina Smith, Rajesh Angireddy, Xiao Min Wang, Erin Weiss, Annick Toutain, Roberto Mendoza-Londono, Lucie Dupuis, Nadirah Damseh, Danita Velasco, Irene Valenzuela, Marta Codina-Solà, Catherine Ziats, Jaclyn Have, Katie Clarkson, Dora Steel, Manju Kurian, Katy Barwick, Diana Carrasco, Aditi I. Dagli, M. J. M. Nowaczyk, Miroslava Hančárová, Šárka Bendová, Darina Prchalova, Zdeněk Sedláček, Alica Baxová, Catherine Bearce Nowak, Jessica Douglas, Wendy K. Chung, Nicola Longo, Konrad Platzer, Chiara Klöckner, Luisa Averdunk, Dagmar Wieczorek, Ilona Krey, Christiane Zweier, Andre Reis, Tugce Balci, Marleen Simon, Hester Y. Kroes, Antje Wiesener, Georgia Vasileiou, Nikolaos M. Marinakis, Danai Veltra, Christalena Sofocleous, Konstantina Kosma, Joanne Traeger Synodinos, Konstantinos A. Voudris, Marie-Laure Vuillaume, Paul Gueguen, Nicolas Derive, Estelle Colin, Clarisse Battault, Billie Au, Martin Delatycki, Mathew Wallis, Lyndon Gallacher, Fatma Majdoub, Noor Smal, Sarah Weckhuysen, An-Sofie Schoonjans, R. Frank Kooy, Marije Meuwissen, Benjamin T. Cocanougher, Kathryn Taylor, Carolyn E. Pizoli, Marie T. McDonald, Philip James, Elizabeth R. Roeder, Rebecca Littlejohn, Nicholas A. Borja, Willa Thorson, Kristine King, Radka Stoeva, Manon Suerink, Esther Nibbeling, Stephanie Baskin, Gwenaël L. E. Guyader, Julie Kaplan, Candace Muss, Deanna Alexis Carere, Elizabeth J. K. Bhoj, Laura M. Bryant |
| Prispievatelia: | Institut Català de la Salut, [Layo-Carris DE, Durham EL] Department of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. [Lubin EE, Sangree AK, Clark KJ, Gonzalez EM] Department of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [Valenzuela I, Codina-Solà M] Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Medicina Genètica, Vall Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Genetica Klinische Genetica, Child Health |
| Zdroj: | Eur J Hum Genet Scientia Scientia. Dipòsit d'Informació Digital del Departament de Salut instname European journal of human genetics Layo-Carris, Dana E; Lubin, Emily E; Sangree, Annabel K; Clark, Kelly J; Durham, Emily L; Gonzalez, Elizabeth M; Smith, Sarina; Angireddy, Rajesh; Wang, Xiao Min; Weiss, Erin; Mendoza-Londono, Roberto; Dupuis, Lucie; Damseh, Nadirah; Velasco, Danita; Valenzuela, Irene; Codina-Solà, Marta; Ziats, Catherine; Have, Jaclyn; Clarkson, Katie; Steel, Dora; ... (2024). Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals. European journal of human genetics, 32(8), pp. 928-937. Springer Nature 10.1038/s41431-024-01610-1 <http://dx.doi.org/10.1038/s41431-024-01610-1> |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, 0301 basic medicine, PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico, Intellectual disability, Gene, Histones, Genetic heterogeneity, FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo, PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype, Genetics(clinical), Missense mutation, Child, 0303 health sciences, Life Sciences, Neurodegenerative Diseases, 16. Peace & justice, Genomic Rearrangements and Copy Number Variations, 3. Good health, Fenotip, Chemistry, Phenotype, Child, Preschool, Molecular Basis of Rett Syndrome and Related Disorders, Female, Epigenetics, Trastorns del desenvolupament - Aspectes genètics, Adult, Adolescent, 610 Medicine & health, Hypotonia, Adolescent [MeSH], Female [MeSH], Adult [MeSH], Histones/genetics [MeSH], Humans [MeSH], Neurodevelopmental Disorders/pathology [MeSH], Intellectual Disability/genetics [MeSH], 631/208/1516, Neurodegenerative Diseases/pathology [MeSH], Neurodevelopmental Disorders/genetics [MeSH], Neurodegenerative Diseases/genetics [MeSH], Intellectual Disability/pathology [MeSH], 631/208/366, Article, Male [MeSH], Phenotype [MeSH], Child [MeSH], article, Child, Preschool [MeSH], 03 medical and health sciences, Neurodevelopmental disorder, Intellectual Disability, Biochemistry, Genetics and Molecular Biology, Journal Article, Genetics, DISEASES::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability, ENFERMEDADES::afecciones patológicas, signos y síntomas::signos y síntomas::manifestaciones neurológicas::manifestaciones neuroconductuales::discapacidad intelectual, Humans, Discapacitat intel·lectual, Biology, Brain Development, Standards and Guidelines for Genetic Variant Interpretation, Neurodevelopmental Disorders, FOS: Biological sciences, Human medicine, PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders |
| Popis: | Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1–4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1–4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-024-01610-1 |
| DOI: | 10.48350/196319 |
| DOI: | 10.60692/kq2gh-6ta54 |
| DOI: | 10.60692/5ce3q-0nt96 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38678163 https://hdl.handle.net/11351/11842 https://dspace.library.uu.nl/handle/1874/454819 https://hdl.handle.net/1887/4210177 https://hdl.handle.net/10067/2058020151162165141 https://repository.uantwerpen.be/docstore/d:irua:23508 https://boris.unibe.ch/196319/ https://repository.publisso.de/resource/frl:6492310 https://discovery-pp.ucl.ac.uk/id/eprint/10191954/ |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....3ca02bf70df7bdc8d778be5241b9f1cb |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1–4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1–4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research. |
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| ISSN: | 14765438 10184813 |
| DOI: | 10.1038/s41431-024-01610-1 |