[EXOME ANALYSIS - A GAME CHANGER IN PEDIATRICS].

Area of Science:

• Genomics
• Clinical Genetics
• Molecular Diagnostics

Background:

• Exome sequencing has become a primary diagnostic tool in clinical practice, 13 years after the human genome project.
• Hadassah's Department of Genetics pioneered exome analysis in Israeli pediatric departments, analyzing 2600 exomes to date.
• Exome analysis provides rapid, precise, and non-invasive diagnosis for numerous genetic disorders and congenital malformations.

Purpose of the Study:

• To review the application and outcomes of exome sequencing technology in three pediatric departments at Hadassah.
• To highlight the diagnostic yield and clinical utility of exome analysis in a population with a high consanguinity rate.
• To discuss the challenges and ethical considerations associated with exome sequencing, including variant interpretation and incidental findings.

Main Methods:

• Retrospective review of exome analysis cases performed in pediatric departments at Hadassah.
• Analysis of diagnostic yield, particularly in cases with high consanguinity.
• Evaluation of the contribution of exome sequencing to genetic counseling, disease understanding, and patient management.

Main Results:

• Hadassah achieved a 65% diagnostic rate using exome analysis, double the global average, attributed to the unique population.
• Exome sequencing facilitated precise diagnoses, enabling genetic counseling and prevention of serious genetic disorders.
• The study identified challenges in variant interpretation and the ethical implications of incidental findings.

Conclusions:

• Exome sequencing is an effective and valuable diagnostic tool in pediatric genetics, especially in consanguineous populations.
• The technology aids in understanding genetic disorders and improving patient management.
• Addressing the challenges of variant interpretation and ethical concerns is crucial for maximizing the benefits of exome sequencing.