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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Limb-Girdle Muscular Dystrophy and other Myopathy ...
Limb-Girdle Muscular Dystrophy and other Myopathy Patients Diagnostic Yield in Large Cohort of more than 6000 patients
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Pdf Summary
In this study, the researchers utilized a next-generation sequencing (NGS) assay to perform diagnostic muscular dystrophy (MD) panel testing. This approach allowed for the detection of all variant types associated with MD. The comprehensive NGS panel proved to be beneficial in identifying subtypes of limb-girdle muscular dystrophy (LGMD) as well as other myopathies that have clinical features overlapping with LGMD. The study found an increased prevalence of genetically confirmed Oculopharyngeal Muscular Dystrophy (OPMD), VCP related inclusion body myopathy, and other dominant overlapping MDs.<br /><br />The implementation of this NGS-based multi-gene panel in a large cohort of over 6,000 patients resulted in a molecular diagnosis for 19.6% of cases examined. Copy number variants (CNVs) were identified in 95 of these cases, with different sizes of CNVs being successfully detected in various MD genes. Major genes contributing to LGMD included CAPN3, DYSF, GAA, ANO5, and FKRP. Genes associated with other overlapping MD subtypes included PABPN1, VCP, MYOT, LDB3, COL6A1, FLNC, and DNAJB6.<br /><br />The researchers used a custom targeted sequence capture and NGS to analyze the genetic variants. Variants were assessed using a proprietary analysis and interpretation pipeline called ODIN, and variant interpretations were performed according to the American College of Medical Genetics (ACMG) standards and guidelines. CNV analysis was conducted using Biodiscovery's NxClinical software.<br /><br />The study findings provide valuable insights into the genetic spectrum underlying LGMDs and other overlapping MDs. The use of NGS-based panel testing and CNV analysis proved to be instrumental in identifying rare MD subtypes. This research has the potential to attract more attention and resources towards these rare disorders, with the hope of developing targeted therapies and improving patient outcomes.<br /><br />Figure 1 of the study displays major LGMD subtypes and overlapping MD subtypes that were identified. Additionally, Figure 2 showcases examples of genetic variants found in patients with LGMD and muscular dystrophy. The study was conducted by Babi Ramesh Reddy Nallamilli, Yinghong Pan, Lakshmanan Jagannathan, Vinish Ramachander, and Madhuri Hegde from PerkinElmer Genomics in Atlanta, GA.
Asset Subtitle
Presenting Author - Babi Nallamilli, PhD, FACMG; Co-Author - Yinghong Pan, PhD; Co-Author - Jagannathan Lakshmanan, PhD; Co-Author - Vinish Ramachander, PhD; Co-Author - Madhuri Hegde, PhD, FACMG;
Meta Tag
Genetic Testing
Musculoskeletal system
NextGen Sequencing
Co-Author
Yinghong Pan, PhD
Co-Author
Jagannathan Lakshmanan, PhD
Co-Author
Vinish Ramachander, PhD
Co-Author
Madhuri Hegde, PhD, FACMG
Presenting Author
Babi Nallamilli, PhD, FACMG
Keywords
next-generation sequencing
diagnostic muscular dystrophy
LGMD subtypes
Oculopharyngeal Muscular Dystrophy
VCP related inclusion body myopathy
copy number variants
MD genes
targeted sequence capture
ACMG standards and guidelines
rare MD subtypes
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