2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Sequence and copy number variant detection in autosomal recessive conditions utilizing tiered-testing approach

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A tiered-testing approach that combines chromosomal microarray analysis (CMA) and whole exome sequencing (WES) is effective in diagnosing autosomal recessive neurodevelopmental disorders. In a case series presented by Bionano Laboratories, it is shown that both copy number variants and sequence variants are important for a comprehensive evaluation of these disorders. The first-line diagnostic test is CMA, which detects copy number variants. However, it has limitations in terms of detection rates. WES is used as a subsequent test and helps to detect sequence variants. The combination of both tests allows for broad genomic detection and adheres to current medical guidelines.<br /><br />The significance of this tiered approach lies in its ability to provide a more complete evaluation of multiple genetic variants, leading to better clinical management. The cases presented in the study demonstrate how this approach can optimize clinical outcomes and shorten diagnostic odysseys for individuals with neurodevelopmental disorders. The study underscores the importance of accurate detection of both copy number and sequence variants in the evaluation of autosomal recessive disorders.<br /><br />The study presents five cases of individuals with neurodevelopmental disorders who were diagnosed using the tiered-testing approach. The cases involve individuals with conditions such as limb-girdle muscular dystrophy, oculocutaneous albinism, Cohen syndrome, WWOX-related disorder, and juvenile Parkinson disease. In each case, both copy number variants and sequence variants were detected, leading to an autosomal recessive diagnosis.<br /><br />Overall, the study highlights the efficacy of the reflexive, guideline-driven testing strategy in the evaluation of autosomal recessive neurodevelopmental disorders. By combining CMA and WES, this approach allows for comprehensive genomic detection while adhering to current medical guidelines.

Asset Subtitle

Co-Author - Abby Stevens, MS; Co-Author - Anjana Varma, MS, MSGC; Presenting Author - Megan Martin, MS, CGC; Co-Author - Colleen G. Bilancia, PhD;

Meta Tag

array CGH

Chromosomal Abnormalities

Clinical Applications of Molecular Cytogenetics

Clinical Cytogenetics

Exome sequencing

Genetic Testing

Microarray

Co-Author Abby Stevens, MS

Co-Author Anjana Varma, MS, MSGC

Co-Author Colleen G. Bilancia, PhD

Presenting Author Megan Martin, MS, CGC

Keywords

tiered-testing approach

chromosomal microarray analysis

CMA

whole exome sequencing

WES

autosomal recessive neurodevelopmental disorders

copy number variants

sequence variants

genomic detection

medical guidelines