Clinical Testing for Genetic Conditions

Area of Science:

• Reproductive Medicine
• Clinical Genetics
• Genomic Diagnostics

Background:

• Reproductive genetics has evolved from cytogenetics to comprehensive genomic analysis.
• Current diagnostics address sequence and structural variations for various reproductive and pediatric conditions.

Purpose of the Study:

• To present a pragmatic algorithm for ordering genome-wide diagnostic tests.
• To optimize the diagnostic pathway for infertility, pregnancy loss, fetal anomalies, and pediatric diseases.

Main Methods:

• Integration of karyotyping, chromosomal microarray (CMA), exome/genome sequencing (GS), long-read sequencing, and optical genome mapping (OGM).
• A reflexive testing pathway linking various genomic modalities.
• Development of a pragmatic algorithm for test ordering.

Main Results:

• Karyotyping is essential for aneuploidy and balanced rearrangements.
• CMA excels in detecting submicroscopic copy number variants.
• Trio exome/GS and advanced structural platforms like OGM enhance diagnostic yield for complex cases.
• Long-read sequencing and OGM resolve complex structural variants and provide genome-wide structural views.

Conclusions:

• The integrated approach supports precise diagnoses and recurrence risk estimation.
• The proposed algorithm aims to reduce testing time and serial testing.
• Enhanced genetic diagnostics improve patient counseling and reproductive planning.