High resolution array analysis: diagnosing pregnancies with abnormal ultrasound findings

Area of Science:

• Genomics
• Prenatal Diagnostics
• Medical Genetics

Background:

• Genome-wide high-resolution array analysis is an emerging diagnostic tool for intellectual disability and congenital anomalies, identifying novel microdeletion and microduplication syndromes.
• The diagnostic utility of high-resolution array comparative genomic hybridization (aCGH) for prenatal testing requires systematic evaluation.

Purpose of the Study:

• To assess the diagnostic yield of high-resolution array genomic hybridization analysis in prenatal samples with abnormal ultrasound findings and normal karyotypes.

Main Methods:

• 106 prenatal samples with abnormal ultrasounds and normal karyotypes were analyzed using the Affymetrix GeneChip 6.0 array.
• Rare DNA copy number variations (CNVs) were classified based on size, genomic location, and comparison to 3000 control samples.

Main Results:

• 35 rare CNVs were identified, with 10 (9%) deemed likely pathogenic (5 syndromic, 5 novel).
• 12 CNVs were common in controls and likely benign; 13 were of unknown significance.
• Cryptic mosaicism for trisomy 10, loss of heterozygosity (LOH), and triploidy detection were also identified.

Conclusions:

• High-resolution array testing, when carefully implemented, can benefit at least 10% of obstetric patients presenting with abnormal ultrasound findings and normal karyotype results.
• Array analysis provides valuable diagnostic information beyond standard karyotyping in select prenatal cases.