2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-De novo missense variants in ZBTB47 cause a neurodevelopmental phenotype of developmental delays, seizures, and possible movement abnormalities

De novo missense variants in ZBTB47 cause a neurodevelopmental phenotype of developmental delays, seizures, and possible movement abnormalities
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This document summarizes a study about a newly identified neurodevelopmental disorder caused by variants in the ZBTB47 gene. The study identified five unrelated individuals with de novo missense variants in ZBTB47, all of whom shared overlapping symptoms including global developmental delay, intellectual disability, hypotonia, seizure disorder, and abnormal movements. The variants affected conserved amino acid residues in ZBTB47's zinc finger domains, suggesting a potential role in neurodevelopmental regulation. The individuals in the study also exhibited other medical problems such as cardiovascular and gastrointestinal issues, as well as dysmorphic features. The study findings suggest that ZBTB47 variants characterize a new neurodevelopmental disorder. The variants identified were NM_145166.3:c.2039A>G;p.E680G in patient 1 and NM_145166.3:c.1429G>A;p.E477K in patients 2-5. Both variants impact conserved amino acid residues and are predicted to be pathogenic based on bioinformatic analysis. This research adds to the growing body of knowledge about the impact of zinc finger transcription factors on neurodevelopmental disorders and expands the understanding of the genetic causes underlying these conditions. The study highlights the importance of exome sequencing in identifying rare genetic variants associated with neurodevelopmental disorders. Further research is needed to fully understand the mechanisms by which ZBTB47 variants contribute to the neurodevelopmental phenotype observed in the study participants. This information will be crucial in developing targeted therapies and interventions to improve the lives of individuals affected by this disorder.

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Presenting Author - Scott K. Ward, MD; Co-Author - Lindsay C. Burrage; Co-Author - Jill A. Rosenfeld, MS; Co-Author - Carlos A. Bacino, MD, FACMG; Co-Author - Brendan Lee, MD, PhD; Co-Author - William J. Craigen, MD, PhD; Co-Author - Lisa T. Emrick, MD; Co-Author - Kristen Fisher, DO; Co-Author - Alexandrea Wadley, MMSc; Co-Author - Chun-Hui Tsai, MD, MSc; Co-Author - Paul J. Benke, MD, PhD; Co-Author - Maria J. Guillen Sacoto, MD; Co-Author - Kimberly Glaser, MS; Co-Author - David R. Murdock, MD; Co-Author - Luis Rohena, MD, PhD; Co-Author - K.E.M. Diderich, MD, PhD; Co-Author - Kimberly M. Houck, MD; Co-Author - H.T. Bruggenwirth, PhD;

Meta Tag

Brain/Nervous System

Clinical History

Cognitive Disorders

Delineation of Diseases

Exome sequencing

Genetic Testing

Genotype-Phenotype Correlations

Identification of Disease Genes

Intellectual disability

Phenotype

Phenotypic delineation of disorders

Variant Detection

Co-Author Lindsay C. Burrage

Co-Author Jill A. Rosenfeld, MS

Co-Author Carlos A. Bacino, MD, FACMG

Co-Author Brendan Lee, MD, PhD

Co-Author William J. Craigen, MD, PhD

Co-Author Lisa T. Emrick, MD

Co-Author Kristen Fisher, DO

Co-Author Alexandrea Wadley, MMSc

Co-Author Chun-Hui Tsai, MD, MSc

Co-Author Paul J. Benke, MD, PhD

Co-Author Maria J. Guillen Sacoto, MD

Co-Author Kimberly Glaser, MS

Co-Author David R. Murdock, MD

Co-Author Luis Rohena, MD, PhD

Co-Author K.E.M. Diderich, MD, PhD

Co-Author Kimberly M. Houck, MD

Co-Author H.T. Bruggenwirth, PhD

Presenting Author Scott K. Ward, MD

Keywords

neurodevelopmental disorder

ZBTB47 gene

variants

missense variants

global developmental delay

intellectual disability

hypotonia

seizure disorder

abnormal movements

zinc finger domains