Neurodevelopmental and other phenotypes recurrently associated with heterozygous BAZ2B loss‐of‐function variants
American Journal of Medical Genetics Part A, vol. 194, pp. e63445
Abstract
The bromodomain adjacent to zinc finger 2B (BAZ2B) gene encodes a chromatin remodeling protein that has been shown to perform a variety of regulatory functions. It has been proposed that loss of BAZ2B function is associated with neurodevelopmental phenotypes, and some recurrent structural birth defects and dysmorphic features have been documented among individuals carrying heterozygous loss-of-function BAZ2B variants. However, additional evidence is needed to confirm that these phenotypes are attributable to BAZ2B deficiency. Here, we report 10 unrelated individuals with heterozygous deletions, stop-gain, frameshift, missense, splice junction, indel, and start-loss variants affecting BAZ2B. These included a paternal intragenic deletion and a maternal frameshift variant that were inherited from mildly affected or asymptomatic parents. The analysis of molecular and clinical data from this cohort, and that of individuals previously reported, suggests that BAZ2B haploinsufficiency causes an autosomal dominant neurodevelopmental syndrome that is incompletely penetrant. The phenotypes most commonly seen in association with loss of BAZ2B function include developmental delay, intellectual disability, autism spectrum disorder, speech delay-with some affected individuals being non-verbal-behavioral abnormalities, seizures, vision-related issues, congenital heart defects, poor fetal growth, and an indistinct pattern of dysmorphic features in which epicanthal folds and small ears are particularly common.
Authors 23
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Affiliation as printed
Department of Molecular and Human Genetics, Baylor College of Medicine Houston Texas USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
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Baylor College of Medicine · Texas Children's Hospital
Affiliation as printed
Department of Molecular and Human Genetics, Baylor College of Medicine Houston Texas USA
Texas Children's Hospital Houston Texas USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Texas Children's Hospital, Houston, Texas, USA
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Kaiser Permanente · Kaiser Permanente Oakland Medical Center
Affiliation as printed
Department of Medical Genetics, Kaiser Permanente Oakland Medical Center Oakland California USA
Department of Medical Genetics, Kaiser Permanente Oakland Medical Center, Oakland, California, USA
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Affiliation as printed
UF6254 Innovation en Diagnostic Genomique des Maladies Rares Dijon France
Équipe Génétique des Anomalies du Développement (GAD) Dijon France
UF6254 Innovation en Diagnostic Genomique des Maladies Rares, Dijon, France
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Université de Bourgogne · Centre Georges François Leclerc · Université Bourgogne Franche-Comté · Genomic and Immunotherapy Medical Institute
Affiliation as printed
Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER Dijon France
Genomic and Immunotherapy Medical Institute Dijon France
Platform of Transfer in Cancer Biology, Georges François Leclerc Cancer Center – UNICANCER Dijon France
Université Bourgogne Franche‐Comté Dijon France
Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER Dijon France
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Affiliation as printed
Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs”, Centre de Génétique, FHU‐TRANSLAD Dijon France
Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU‐TRANSLAD Dijon France
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Centre National de la Recherche Scientifique · Inserm · Centre Hospitalier Universitaire de Nantes · Institut du Thorax
Affiliation as printed
Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale Nantes France
INSERM, CNRS UNIV Nantes, l'institut du thorax Nantes France
Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale Nantes France
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University Medical Center Utrecht
Affiliation as printed
Department of Genetics University Medical Center Utrecht Utrecht The Netherlands
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
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University of California, Davis
Affiliation as printed
Division of Genomic Medicine, Department of Pediatrics, MIND Institute University of California, Davis Sacramento California USA
Division of Genomic Medicine, Department of Pediatrics, MIND Institute, University of California, Davis, Sacramento, California, USA
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Cincinnati Children's Hospital Medical Center · University of Cincinnati
Affiliation as printed
Cincinnati Children's Hospital Medical Center Department of Psychiatry Cincinnati Ohio USA
Cincinnati Children's Hospital Medical Center, Department of Human Genetics Cincinnati Ohio USA
University of Cincinnati College of Medicine Department of Pediatrics Cincinnati Ohio USA
Cincinnati Children's Hospital Medical Center Department of Psychiatry, Cincinnati, Ohio, USA
Cincinnati Children's Hospital Medical Center, Department of Human Genetics, Cincinnati, Ohio, USA
University of Cincinnati College of Medicine Department of Pediatrics, Cincinnati, Ohio, USA
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Cincinnati Children's Hospital Medical Center
Affiliation as printed
Cincinnati Children's Hospital Medical Center, Department of Human Genetics Cincinnati Ohio USA
Cincinnati Children's Hospital Medical Center, Department of Human Genetics, Cincinnati, Ohio, USA
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Affiliation as printed
Clinical Genomics Program, GeneDx Gaithersburg Maryland USA
Clinical Genomics Program, GeneDx, Gaithersburg, Maryland, USA
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University of Colorado Anschutz
Affiliation as printed
Department of Pediatrics University of Colorado Aurora Colorado USA
Department of Pediatrics, University of Colorado, Aurora, Colorado, USA
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University of Colorado Anschutz
Affiliation as printed
Department of Pediatrics University of Colorado Aurora Colorado USA
Department of Pediatrics, University of Colorado, Aurora, Colorado, USA
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University of Colorado Anschutz
Affiliation as printed
Department of Pediatrics University of Colorado Aurora Colorado USA
Department of Pediatrics, University of Colorado, Aurora, Colorado, USA
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Haga Hospital · Juliana Kinderziekenhuis
Affiliation as printed
Department of Paediatrics, Juliana Children's Hospital, HAGA Medical Center the Hague The Netherlands
Department of Paediatrics, Juliana Children's Hospital, HAGA Medical Center, the Hague, The Netherlands
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Mariëtte J.V. Hoffer Aachen Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands Department of Clinical Genetics
Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Inge M. M. Lakeman Aachen Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands Department of Clinical Genetics
Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Université de Bourgogne · Université Bourgogne Franche-Comté
Affiliation as printed
Centre de Genetique Humaine Universite de Bourgogne Franche‐Comte France
Centre de Genetique Humaine, Universite de Bourgogne Franche-Comte, France
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Affiliation as printed
Department of Brain Sciences, Imperial College London and Portland Hospital HCA International London United Kingdom
Department of Brain Sciences, Imperial College London and Portland Hospital HCA International, London, United Kingdom
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Baylor College of Medicine · Baylor Genetics
Affiliation as printed
Baylor Genetics Houston Texas USA
Department of Molecular and Human Genetics, Baylor College of Medicine Houston Texas USA
Baylor Genetics, Houston, Texas, USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
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Baylor College of Medicine · Texas Children's Hospital
Affiliation as printed
Department of Molecular and Human Genetics, Baylor College of Medicine Houston Texas USA
Texas Children's Hospital Houston Texas USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Texas Children's Hospital, Houston, Texas, USA
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Daryl A. Scott corresponding
Baylor College of Medicine · Texas Children's Hospital
Affiliation as printed
Department of Molecular Physiology and Biophysics, Baylor College of Medicine Houston Texas USA
Department of Molecular and Human Genetics, Baylor College of Medicine Houston Texas USA
Texas Children's Hospital Houston Texas USA
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Texas Children's Hospital, Houston, Texas, USA
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