2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-<em>Functional Studies in ADAMTSL2-Related Geleophysic Dysplasia Provide Insights Into Pathogenesis and Potential Treatment Targets </em>

Functional Studies in ADAMTSL2-Related Geleophysic Dysplasia Provide Insights Into Pathogenesis and Potential Treatment Targets
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This study focuses on Geleophysic Dysplasia (GD), a genetic disorder that affects various aspects of the body, including facial features, stature, joint mobility, and cardiovascular and respiratory function. The researchers used human skin fibroblasts from patients with different forms of GD and performed genome-wide expression profiling to identify differences in gene expression. They also used knock-in mouse models to study the effects of specific mutations in the ADAMTSL2 gene, which is associated with GD. The researchers characterized the mice by measuring survival, weight, anatomical features, and cardiovascular and respiratory function. They also conducted a drug screening to find potential treatments for GD using an FDA-approved compound library. The study found that Adamtsl2 is central to the development of GD and that different mutations in the gene result in varying degrees of phenotypic severity. The researchers also discovered that the secretion of key extracellular matrix proteins is impaired in GD fibroblasts and that the RNA expression profile is similar to that of fibroblasts with mutations in the FBN1 gene, which is associated with other genetic disorders. Additionally, the study found that mice with ADAMTSL2 mutations exhibit skeletal abnormalities and altered lung and heart function. Overall, this research provides insights into the pathogenesis of GD and identifies potential treatment targets. The study was supported by the Al Rashid Family and highlights the importance of personalized medicine in addressing rare genetic disorders like GD.

Asset Subtitle

Presenting Author - Vladimir Camarena, MD PhD; Co-Author - Alejo A. Morales, phD; Co-Author - Monique M. Williams, MD; Co-Author - Mohammad F. Zafeer, phD; Co-Author - Okan V. Kilic, MD; Co-Author - Ali Kamiar, Pharm.D; Co-Author - Monica Rasmuseen, MD PhD student; Co-Author - LéShon C. Peart, MD; Co-Author - Guney Bademci, MD, FACMG; Co-Author - Deborah S. Barbouth; Co-Author - Sarah Smithson, MD; Co-Author - Lina A. Shehadeh, phD; Co-Author - Gaofeng Wang, phD; Co-Author - Katherina Walz, phD; Co-Author - Mustafa Tekin;

Meta Tag

Bone/Joint Abnormalities

Cardiac/circulatory disorders

Cardiovascular System

Delineation of Diseases

Genotype-Phenotype Correlations

Model Organisms

Molecular Pathophysiology

Morphogenesis

Musculoskeletal system

Pathogenesis

Phenotype

Phenotypic delineation of disorders

Pulmonary/respiratory malformations

Respiratory System

Therapy

Transgenic Model

Variant Detection

Co-Author Alejo A. Morales, phD

Co-Author Monique M. Williams, MD

Co-Author Mohammad F. Zafeer, phD

Co-Author Okan V. Kilic, MD

Co-Author Ali Kamiar, Pharm.D

Co-Author Monica Rasmuseen, MD PhD student

Co-Author LéShon C. Peart, MD

Co-Author Guney Bademci, MD, FACMG

Co-Author Deborah S. Barbouth

Co-Author Sarah Smithson, MD

Co-Author Lina A. Shehadeh, phD

Co-Author Gaofeng Wang, phD

Co-Author Katherina Walz, phD

Co-Author Mustafa Tekin

Presenting Author Vladimir Camarena, MD PhD

Keywords

Geleophysic Dysplasia

genetic disorder

facial features

stature

joint mobility

cardiovascular function

respiratory function

gene expression

mutations

treatment targets