Clinical utility of the X-chromosome array

Area of Science:

• Genetics
• Genomics
• Clinical Diagnostics

Background:

• X-chromosome array platforms have been primarily used for intellectual disability evaluations.
• The clinical utility of X-chromosome arrays in diverse scenarios requires further investigation.

Purpose of the Study:

• To retrospectively analyze the clinical utility of X-chromosome arrays across various patient indications.
• To assess the diagnostic yield and effectiveness of X-chromosome arrays in identifying copy number variants, especially for X-linked conditions.

Main Methods:

• Retrospective analysis of 59 X-chromosome array studies.
• Patients categorized into four groups based on testing indications: ASDs/DD/ID with/without family history, breakpoint definition, and suspected X-linked conditions.
• Analysis of detected copy number variants and their clinical significance (pathogenic, benign, uncertain).

Main Results:

• Overall, 42% (25/59) of studies detected copy number variants.
• Pathogenic or likely pathogenic variants were identified in 27% (16/59) of cases.
• The X-chromosome array showed a 63% (12/19) diagnostic yield for suspected X-linked conditions, aiding in evaluation and risk assessment.

Conclusions:

• X-chromosome arrays frequently detect clinically relevant genomic alterations on the X chromosome.
• The array offers advantages for evaluating specific X-linked conditions and provides utility in risk assessment for affected families.
• Careful interpretation and clinical correlation are essential for determining the significance of detected genomic changes.