Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Autor: Layo-Carris DE; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Lubin EE; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sangree AK; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Clark KJ; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Durham EL; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Gonzalez EM; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Smith S; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Angireddy R; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Wang XM; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Weiss E; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Toutain A; Service de Génétique, CHU de Tours, Tours, France.; UMR1253, iBrain, Inserm, University of Tours, Tours, France., Mendoza-Londono R; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Dupuis L; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Damseh N; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Velasco D; Children's Nebraska, University of Nebraska Medical Center, Omaha, NE, USA., Valenzuela I; Department of Clinical and Molecular Genetics and Rare Disease Unit Hospital Vall d'Hebron, Barcelona, Spain.; Medicine Genetics Group, Vall Hebron Research Institute, Barcelona, Spain., Codina-Solà M; Department of Clinical and Molecular Genetics and Rare Disease Unit Hospital Vall d'Hebron, Barcelona, Spain.; Medicine Genetics Group, Vall Hebron Research Institute, Barcelona, Spain., Ziats C; Shodair Children's Hospital, Helena, MT, USA., Have J; Shodair Children's Hospital, Helena, MT, USA., Clarkson K; Greenwood Genetic Center, Greenwood, SC, USA., Steel D; UCL Great Ormond Street Institute of Child Health, London, UK., Kurian M; UCL Great Ormond Street Institute of Child Health, London, UK., Barwick K; UCL Great Ormond Street Institute of Child Health, London, UK., Carrasco D; Department of Clinical Genetics, Cook Children's Hospital, Fort Worth, TX, USA., Dagli AI; Orlando Health, Arnold Palmer Hospital For Children, Orlando, FL, USA., Nowaczyk MJM; McMaster University Medical Centre, Hamilton, ON, Canada., Hančárová M; Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic., Bendová Š; Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic., Prchalova D; Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic., Sedláček Z; Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic., Baxová A; Charles University First Faculty of Medicine and General University Hospital, Prague, Czech Republic., Nowak CB; Division of Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, MA, USA., Douglas J; Harvard Medical School, Boston, MA, USA., Chung WK; Harvard Medical School, Boston, MA, USA.; Boston Children's Hospital, Boston, MA, USA., Longo N; University of Utah, Salt Lake City, UT, USA., Platzer K; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Klöckner C; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Averdunk L; Institute of Human Genetics, Heinrich-Heine-University Düsseldorf, Medical Faculty, Düsseldorf, Germany., Wieczorek D; Institute of Human Genetics, Heinrich-Heine-University Düsseldorf, Medical Faculty, Düsseldorf, Germany., Krey I; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Zweier C; Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.; Department of Human Genetics, Inselspital Bern, University of Bern, Bern, Switzerland., Reis A; Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany., Balci T; University of Western Ontario, London, ON, Canada., Simon M; Department of Genetics, University Medical Center, Utrecht, Netherlands., Kroes HY; Department of Genetics, University Medical Center, Utrecht, Netherlands., Wiesener A; Department of Genetics, University Medical Center, Utrecht, Netherlands., Vasileiou G; Department of Genetics, University Medical Center, Utrecht, Netherlands., Marinakis NM; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Veltra D; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Sofocleous C; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Kosma K; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Traeger Synodinos J; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece., Voudris KA; Second Department of Paediatrics, University of Athens, 'P & A Kyriakou' Children's Hospital, Athens, Greece., Vuillaume ML; Service de Génétique, CHU de Tours, Tours, France.; UMR1253, iBrain, Inserm, University of Tours, Tours, France.; Laboratoire de Biologie Médicale Multi-Sites SeqOIA, Paris, France., Gueguen P; Service de Génétique, CHU de Tours, Tours, France.; UMR1253, iBrain, Inserm, University of Tours, Tours, France.; Laboratoire de Biologie Médicale Multi-Sites SeqOIA, Paris, France., Derive N; Laboratoire de Biologie Médicale Multi-Sites SeqOIA, Paris, France., Colin E; Service de Génétique Médicale, CHU d'Angers, Angers, France., Battault C; Service de Génétique Médicale, CHU d'Angers, Angers, France., Au B; University of Calgary, Calgary, AB, Canada., Delatycki M; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia., Wallis M; Tasmanian Clinical Genetics Service, Tasmanian Health Service, Hobart, TAS, Australia.; School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia., Gallacher L; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia., Majdoub F; Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, Antwerp, Belgium.; Applied and Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Sfax, Tunisia., Smal N; Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, Antwerp, Belgium.; Applied and Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Weckhuysen S; Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, Antwerp, Belgium.; Applied and Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Department of Pediatric Neurology, University Hospital Antwerp, Antwerp, Belgium.; Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium.; NEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium., Schoonjans AS; Department of Pediatric Neurology, University Hospital Antwerp, Antwerp, Belgium.; Department of Pediatrics, Duke University Hospital, Durham, NC, USA., Kooy RF; Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, Belgium., Meuwissen M; Department of Pediatrics, Duke University Hospital, Durham, NC, USA.; Center of Medical Genetics, Antwerp University Hospital/University of Antwerp, Edegem, Belgium., Cocanougher BT; Department of Pediatrics, Duke University Hospital, Durham, NC, USA., Taylor K; Division of Pediatric Neurology, Duke University Hospital, Durham, NC, USA., Pizoli CE; Division of Pediatric Neurology, Duke University Hospital, Durham, NC, USA., McDonald MT; Division of Medical Genetics, Duke University Hospital, Durham, NC, USA., James P; DMG Children's Rehabilitative Services, Phoenix, AZ, USA., Roeder ER; Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, USA., Littlejohn R; Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, USA., Borja NA; John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Thorson W; John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., King K; Genetics Department, Mary Bridge Children's Hospital, Multicare Health System, Tacoma, WA, USA., Stoeva R; Medical genetics department, Centre Hospitalier, Le Mans, France., Suerink M; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Nibbeling E; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Baskin S; Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., L E Guyader G; Service de Génétique médicale, Centre Labellisé Anomalies du Développement-Ouest Site, Poitiers, France., Kaplan J; Nemours Children's Health, Wilmington, DE, USA., Muss C; Nemours Children's Health, Wilmington, DE, USA., Carere DA; GeneDx, Gaithersburg, MD, USA., Bhoj EJK; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. bhoje@chop.edu.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. bhoje@chop.edu., Bryant LM; Department of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Aug; Vol. 32 (8), pp. 928-937. Date of Electronic Publication: 2024 Apr 27.
DOI: 10.1038/s41431-024-01610-1
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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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