2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Somatic Overgrowth and Vascular Malformation: Clinical Utility of Expanded Panel

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The study conducted by Niambi S. Brewer and Arupa Ganguly focuses on the clinical utility of an expanded panel for identifying somatic overgrowth and vascular malformation disorders. The researchers expanded their Next-generation sequencing (NGS) panel from 8 genes to 34 genes to improve the diagnostic sensitivity. The study included 326 patients from various hospitals across North America.<br /><br />The results showed that the expanded panel increased the diagnostic sensitivity for somatic vascular malformations and overgrowth disorders. However, it was found that diagnostic results were more often identified in cases that submitted affected tissue samples for testing, rather than unaffected tissue samples. Unaffected tissue samples may not be the most optimal germline sample due to low-levels of mosaicism.<br /><br />Overall, the diagnostic yield of the expanded panel was 56.7%, with 181 out of 319 cases resulting in a clinically significant result. The researchers identified 94 unique variants across 218 total variant calls, with PIK3CA variants accounting for 56.9% of reported variants.<br /><br />The study also highlighted the importance of TEK variants, which accounted for 16.1% of reported variants. Double cis activating variants within the TEK protein kinase domain were found to be associated with blue rubber bleb nevus syndrome (BRBN) and were shown to have an additive effect in inducing vascular malformations.<br /><br />The study provides valuable insights into the clinical utility of expanded gene panels for diagnosing somatic overgrowth and vascular malformation disorders. The findings emphasize the importance of obtaining affected tissue samples for testing and highlight specific variants that play a significant role in these disorders. The expanded panel has shown promise in improving diagnostic sensitivity and guiding therapeutic interventions for patients with these disorders.

Asset Subtitle

Presenting Author - Niambi Brewer, PhD; Co-Author - Arupa Ganguly, PhD;

Meta Tag

Genetic Testing

NextGen Sequencing

Co-Author Arupa Ganguly, PhD

Presenting Author Niambi Brewer, PhD

Keywords

clinical utility

expanded panel

somatic overgrowth

vascular malformation disorders

diagnostic sensitivity

tissue samples

diagnostic yield

PIK3CA variants

TEK variants

gene panels