2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Integrating Multiple Genetic Tests Improves the Diagnostic Rate in Genetic Diseases

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The document discusses the use of chromosomal sequencing analysis (CSA) as a diagnostic tool for genetic diseases. The diagnostic yield of CSA, which combines copy number analysis, exome sequencing analysis, absence of heterozygosity (AOH) analysis, and Fragile X syndrome detection, is reported to be 20% in a cohort of 496 cases. The diagnostic rate for exome analysis alone in patients with neurodevelopmental delay or intellectual disability is reported to be 30-50%. The diagnostic rate can be improved by including biological parents in the analysis (TRIO). Fragile X syndrome and uniparental disomy detection are commonly tested in individuals with developmental defects.<br /><br />The diagnostic results of the screened CSA cases are summarized as follows: approximately 7% of cases had large copy number variants, 13% had sequence variants, and 68% of diagnostic variants identified in TRIO cases were de novo. Other findings included homozygous or compound heterozygous variants and variants inherited from an affected parent.<br /><br />The overall diagnostic rate of all cases was 20%, with copy number analysis playing an important role. If parental samples are available, analyzing the whole exome increases the likelihood of a diagnostic finding.<br /><br />The potential impact of CSA is highlighted by the more efficient and faster diagnosis and treatment it offers for patients with unknown genetic diseases. The study emphasizes the importance of integrating multiple genetic tests to improve the diagnostic rate in genetic diseases.<br /><br />Overall, the study demonstrates the effectiveness of CSA in diagnosing genetic diseases and highlights the importance of copy number analysis and the inclusion of parental samples in improving diagnostic yield.

Asset Subtitle

Presenting Author - Elina Nikkola, PhD; Co-Author - Mui Luong, PhD; Co-Author - Harry Gao, PhD, FACMG; Co-Author - Yan Meng, PhD, CGMBS, FACMG; Co-Author - ZhenBin Chen, Ph.D, CGMBS, FACMG;

Meta Tag

Chromosomal Abnormalities

Exome sequencing

Genetic Testing

Co-Author Mui Luong, PhD

Co-Author Harry Gao, PhD, FACMG

Co-Author Yan Meng, PhD, CGMBS, FACMG

Co-Author ZhenBin Chen, Ph.D, CGMBS, FACMG

Presenting Author Elina Nikkola, PhD

Keywords

chromosomal sequencing analysis

diagnostic tool

genetic diseases

copy number analysis

exome sequencing analysis

Fragile X syndrome detection

diagnostic yield

neurodevelopmental delay

TRIO analysis

unknown genetic diseases