2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Discovery of the phenotypic landscape and mechanistic understanding of <em>NAA10</em>-related and <em>NAA15</em>-related neurodevelopmental syndromes, using mouse models and iPSCs

Discovery of the phenotypic landscape and mechanistic understanding of NAA10-related and NAA15-related neurodevelopmental syndromes, using mouse models and iPSCs

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The document is a research poster presentation about Ogden syndrome, a rare genetic disorder characterized by distinct physical features, growth failure, developmental delays, and heart dysfunction. The study aims to understand the phenotypic landscape and underlying mechanisms of NAA10-related and NAA15-related neurodevelopmental syndromes using mouse models and induced pluripotent stem cells (iPSCs).<br /><br />The research team successfully recreated the long QT syndrome phenotype associated with NAA10 variants using patient-derived iPSC-derived cardiomyocytes. Mouse models and iPSC models are essential for studying the phenotypes of genetic disorders. The results suggest that reduced N-terminal acetylation of specific proteins is involved in the pathogenesis of Ogden syndrome.<br /><br />The study also discusses the establishment of Ogden CARES, a patient-centered foundation, to advance research and gene therapy for Ogden syndrome. The researchers continue to discover altered N-terminal acetylation in certain proteins in patient cells compared to controls, which may provide insight into the mechanisms underlying Ogden syndrome.<br /><br />The document provides references for further reading and contact information for inquiries. It also includes figures displaying iPSC modeling for Ogden syndrome and the pleiotropic phenotypes observed in Naa10 knockout mice, including reduced body weight, abnormal physical features, hydrocephaly, hydronephrosis, and abnormal genitalia.<br /><br />Overall, the research poster summarizes the study's findings regarding the phenotypic landscape, mechanistic understanding, and ongoing efforts to advance research and gene therapy for Ogden syndrome.

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Presenting Author - Gholson Lyon, MD PhD; Co-Author - Marall Vedaie, MD; Co-Author - Travis Beisheim, MD; Co-Author - Agnes Park, MD; Co-Author - Elaine Marchi, BA; Co-Author - Leah Gottlieb, PhD; Co-Author - Lois Starr, MD, PhD, FAAP, FACMG; Co-Author - Katherine Sandomirsky, MD; Co-Author - Hanyin Cheng, PhD; Co-Author - Isabelle Preddy, MD; Co-Author - Marcellus Tseng, MD; Co-Author - Quan Li, PhD; Co-Author - Kai Wang, PhD; Co-Author - Maureen Gavin, BA; Co-Author - Karen Amble, BA; Co-Author - Ronen Marmorstein, PhD; Co-Author - Ellen Herr-Israel, PhD; Co-Author - Randie Harpell, BA; Co-Author - Melissa Nashat, DVM; Co-Author - Ning Ma, PhD; Co-Author - Nadjet Belbachir, PhD; Co-Author - Joseph Wu, MD; Co-Author - Tzung-Chien Hsieh, PhD; Co-Author - Peter Krawitz, MD, PhD; Co-Author - Alan F. Rope, MD; Co-Author - Frederick Monsma, Jr, PhD; Co-Author - Josephine Wesely, PhD; Co-Author - Yu-Ren Chen, PhD; Co-Author - Christopher Hunter, BA; Co-Author - Lauren Bauer, BA; Co-Author - Tom Rusielewicz, PhD; Co-Author - Stephen Kneeland, PhD; Co-Author - Cat Lutz; Co-Author - Kathy Snow, PhD; Co-Author - Steve Murray, PhD; Co-Author - Andrea L. Gropman, MD, FAAP, FACMG, FANA; Co-Author - Matthew Whitehead, MD; Co-Author - Andrew Garcia, MS; Co-Author - Fatima Inusa, BA; Co-Author - Joseph Longo, BA; Co-Author - Nicole Fleischer, MBA; Co-Author - David Bolton, PhD; Co-Author - Martin Reese, PhD; Co-Author - Yu Hu, PhD;

Meta Tag

Brain/Nervous System

Clinical History

Cognitive Disorders

Databases

Dysmorphology

Exome sequencing

Eye disorders

Gastrointestinal System

Genetic Testing

Genome sequencing

Genotype-Phenotype Correlations

Intellectual disability

Malformation

Molecular Pathophysiology

Natural History

Phenotype

Phenotypic delineation of disorders

X-Inactivation/X-Linked Disease

Co-Author Marall Vedaie, MD

Co-Author Travis Beisheim, MD

Co-Author Agnes Park, MD

Co-Author Elaine Marchi, BA

Co-Author Leah Gottlieb, PhD

Co-Author Lois Starr, MD, PhD, FAAP, FACMG

Co-Author Katherine Sandomirsky, MD

Co-Author Hanyin Cheng, PhD

Co-Author Isabelle Preddy, MD

Co-Author Marcellus Tseng, MD

Co-Author Quan Li, PhD

Co-Author Kai Wang, PhD

Co-Author Maureen Gavin, BA

Co-Author Karen Amble, BA

Co-Author Ronen Marmorstein, PhD

Co-Author Ellen Herr-Israel, PhD

Co-Author Randie Harpell, BA

Co-Author Melissa Nashat, DVM

Co-Author Ning Ma, PhD

Co-Author Nadjet Belbachir, PhD

Co-Author Joseph Wu, MD

Co-Author Tzung-Chien Hsieh, PhD

Co-Author Peter Krawitz, MD, PhD

Co-Author Alan F. Rope, MD

Co-Author Frederick Monsma, Jr, PhD

Co-Author Josephine Wesely, PhD

Co-Author Yu-Ren Chen, PhD

Co-Author Christopher Hunter, BA

Co-Author Lauren Bauer, BA

Co-Author Tom Rusielewicz, PhD

Co-Author Stephen Kneeland, PhD

Co-Author Cat Lutz

Co-Author Kathy Snow, PhD

Co-Author Steve Murray, PhD

Co-Author Andrea L. Gropman, MD, FAAP, FACMG, FANA

Co-Author Matthew Whitehead, MD

Co-Author Andrew Garcia, MS

Co-Author Fatima Inusa, BA

Co-Author Joseph Longo, BA

Co-Author Nicole Fleischer, MBA

Co-Author David Bolton, PhD

Co-Author Martin Reese, PhD

Co-Author Yu Hu, PhD

Presenting Author Gholson Lyon, MD PhD

Keywords

Ogden syndrome

genetic disorder

NAA10-related neurodevelopmental syndrome

NAA15-related neurodevelopmental syndrome

mouse models

induced pluripotent stem cells

iPSCs

long QT syndrome

N-terminal acetylation

Ogden CARES