Clinical Utility of a Targeted Next-Generation Sequencing Panel for Inherited Platelet Disorders in Children.

Area of Science:

• Genetics
• Hematology
• Pediatrics

Background:

• Inherited platelet disorders (IPDs) are a group of conditions affecting platelet number and function.
• Next-Generation Sequencing (NGS) is a promising tool for diagnosing IPDs.

Purpose of the Study:

• To evaluate the clinical utility and limitations of a targeted NGS panel for diagnosing IPDs in children.
• To assess the diagnostic yield of NGS in pediatric IPD cases.

Main Methods:

• Retrospective analysis of 93 children with suspected IPDs.
• Targeted NGS panel sequencing of 14 IPD-associated genes.
• Variant identification and classification.

Main Results:

• Genetic variants were identified in 30 patients (32.3%), with 15 novel variants found across 11 genes.
• Most variants were identified in ITGB3, GP1BA, and ADAMTS13 genes.
• The majority of variants were classified as variants of uncertain significance (VUS) (64.9%), followed by likely pathogenic (27%) and pathogenic (8.1%).

Conclusions:

• NGS aids in identifying genetic causes, risk assessment, and management of IPDs, including genetic counseling.
• The high prevalence of VUS highlights the need for a multidisciplinary approach for accurate interpretation of NGS results in pediatric IPD diagnosis.