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: MP4

Video Transcription

Video Summary

In this video, Dr. Jorge Granadillo and Dan Wegner from Washington University present a case study on the integration of genome-wide methylation analysis with clinical genetic testing and genome sequencing. The patient in question is a five-year-old male with features of CHARGE syndrome, a multiple congenital anomaly syndrome. The initial genetic testing including chromosome microarray, CHD7 sequencing, and whole-exome sequencing did not yield a diagnosis. The patient underwent further evaluation, which included a temporal bone CT scan to assess inner ear abnormalities and an HCG stimulation test to evaluate testicular function. The patient's clinical features were consistent with CHARGE syndrome, and subsequent genome-wide methylation analysis revealed a methylation pattern consistent with CHD7-associated epigenetic signature. This led to the identification of a de novo 15-base pair deletion in intron 4 of the CHD7 gene, which disrupted the native 3' splice site and activated an alternative upstream splice site. The deletion was confirmed by Sanger sequencing. The study highlights the importance of comprehensive phenotyping and the integration of different genetic techniques for accurate molecular diagnosis in patients with CHARGE syndrome. The case also emphasizes the potential value of genome-wide methylation analysis in identifying epigenetic patterns and guiding further genetic analysis. The video was presented by Dr. Jorge Granadillo and Dan Wegner at a case conference organized by the ACMG Education Committee.

Keywords

genome-wide methylation analysis

clinical genetic testing

genome sequencing

CHARGE syndrome

chromosome microarray

CHD7 sequencing

whole-exome sequencing

epigenetic patterns

molecular diagnosis