2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Fabry Disease: Genotype/Phenotype Correlations for 17 Novel <em>GLA</em> Mutations By GLA Activity & Plasma Lyso-Gb3 Levels

Pdf Summary

The study conducted genetic analysis on a 48-year-old male and identified a deletion of exons 2-5 in the GLA gene, confirming it through OGT exome array and Sanger sequencing. The research aimed to establish genotype-phenotype correlations for 17 novel GLA mutations related to Fabry disease. They used molecular genetics, biochemical and clinical phenotyping to diagnose and classify these variants effectively. The FD testing expertise of the authors supported their ability to provide enhanced phenotype-guided interpretation for GLA genetic variants.<br /><br />Fabry disease is a rare X-linked lysosomal disorder caused by pathogenic variants in the GLA gene, resulting in reduced GLA enzyme activity. Plasma lyso-Gb3 levels serve as a diagnostic and therapeutic biomarker for the disease. The study sequenced the GLA gene using Next-Generation Sequencing (NGS) in over 1,400 subjects and measured GLA enzyme activity and lyso-Gb3 levels using standardized methods.<br /><br />The objectives of the study were to determine the pathogenicity of 17 novel GLA mutations, annotate their significance through biochemical evidence, and correlate the results with clinical symptoms and family history to identify the disease phenotype. The paper includes tables and figures presenting the identified novel GLA variants in newborn screening and diagnostic testing cases, as well as the genetic and biochemical characteristics of these variants.<br /><br />In summary, the study successfully characterized novel GLA variants and provided insights into their pathogenicity and correlation with Fabry disease phenotypes. The integration of molecular genetics, biochemical analysis, and clinical phenotyping proved to be an effective approach in diagnosing and classifying these variants.

Asset Subtitle

Co-Author - Neal Cody, PhD; Presenting Author - Yu Leng Phua, PhD, FACMG; Co-Author - Wenjiao Li, PhD; Co-Author - Irina Nazarenko, MSc; Co-Author - Brandon Stauffer, PhD; Co-Author - Hongjie Chen, PhD/FACMG; Co-Author - Jing Xiao, PhD; Co-Author - Lisa Edelmann, PhD, FACMG; Co-Author - Ruth Kornreich, PhD, FACMG; Co-Author - Chunli Yu, MD; Co-Author - Robert J. Desnick, MD, PhD;

Meta Tag

Biochemical genetics

Lysosomal Diseases

Co-Author Neal Cody, PhD

Co-Author Wenjiao Li, PhD

Co-Author Irina Nazarenko, MSc

Co-Author Brandon Stauffer, PhD

Co-Author Hongjie Chen, PhD/FACMG

Co-Author Jing Xiao, PhD

Co-Author Lisa Edelmann, PhD, FACMG

Co-Author Ruth Kornreich, PhD, FACMG

Co-Author Chunli Yu, MD

Co-Author Robert J. Desnick, MD, PhD

Presenting Author Yu Leng Phua, PhD, FACMG

Keywords

genetic analysis

deletion

GLA gene

Fabry disease

molecular genetics

biochemical analysis

clinical phenotyping

pathogenic variants

GLA enzyme activity

disease phenotype