[Application of chromosome microarray analysis in 489 children with developmental delay/intellectual disability]

Area of Science:

• Genetics
• Developmental Biology
• Medical Diagnostics

Background:

• Developmental delay/intellectual disability (DD/ID) affects a significant portion of the pediatric population.
• Identifying the genetic etiology of DD/ID is crucial for diagnosis, prognosis, and genetic counseling.
• Conventional karyotyping has limitations in detecting smaller chromosomal abnormalities.

Purpose of the Study:

• To evaluate the diagnostic yield of chromosome microarray analysis (CMA) in children with DD/ID.
• To determine the types and frequency of pathogenic copy number variants (CNVs) identified by CMA.
• To assess the utility of CMA in identifying microdeletion/microduplication syndromes and de novo CNVs.

Main Methods:

• Recruitment of 489 children with DD/ID and normal karyotypes.
• DNA extraction and hybridization using Affymetrix CytoScan 750K array.
• Analysis of array data using CHAS v2.0 software.

Main Results:

• Pathogenic CNVs were identified in 25.8% of cases (126/489).
• CMA detected microdeletion/microduplication syndromes in 79 cases, including specific syndromes like 15q24 microdeletion.
• Forty-seven cases revealed de novo pathogenic CNVs, with potential candidate genes for DD/ID identified.

Conclusions:

• CMA is a highly effective tool for diagnosing the genetic causes of DD/ID.
• CMA surpasses conventional karyotyping in detecting clinically significant chromosomal abnormalities.
• The study identified potential candidate genes associated with DD/ID, warranting further investigation.