View Only- Integration of Genome: Wide Methylation Analysis with Transcription Analysis and Genome Sequencing Enables Molecular Diagnosis in a Patient with CHARGE syndrome-View Only- Integration of Genome: Slides

View Only- Integration of Genome: Slides

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The ACMG Genomics Case Conference took place at Washington University in St. Louis and focused on the integration of genome-wide methylation analysis with transcription analysis and genome sequencing for molecular diagnosis. The conference is intended for healthcare professionals specializing in clinical genetics and genomics. <br /><br />The presenters, Jorge L Granadillo, Daniel Wegner, and Tomi Toler, disclosed no financial conflicts. The presenters provided information on the clinical features of CHARGE syndrome and the limitations of current genetic testing methods. They discussed the case of a 5-year-old male with features of CHARGE syndrome that had non-diagnostic clinical molecular testing. <br /><br />The patient had various anomalies, including global developmental delay, optic nerve coloboma, hearing loss, and bicuspid aortic valve. Previous genetic evaluations, including chromosomal microarray analysis, CHD7 sequencing, and cerebellar/pontocerebellar gene panel testing, had been unremarkable. However, re-analysis of exome sequencing data identified a de novo variant in CHD7 that was missed previously.<br /><br />In addition to genomic sequencing, the patient underwent genome-wide methylation analysis, which confirmed an abnormal methylation pattern consistent with CHD7-associated epigenetic signature. This supported the diagnosis of CHARGE syndrome. RNA studies further confirmed the pathogenicity of the variant.<br /><br />The case highlighted the importance of integrating various genetic techniques for accurate diagnosis. It also emphasized that up to 10% of patients with CHARGE syndrome may have no known genetic cause. The conference provided valuable insights into the diagnosis and management of genetically influenced health problems. A recording of the conference is available in the ACMG Genetics Academy for further reference.

Keywords

ACMG Genomics Case Conference

Washington University in St. Louis

genome-wide methylation analysis

transcription analysis

genome sequencing

molecular diagnosis

clinical genetics

genomics

CHARGE syndrome

genetic testing methods