The advantages and disadvantages of chromosomal microarrays are highlighted in a recent article and a related editorial (NEJM 2012; 367: 2175-84, 2249-51).
Chromosomal microarrays can detect almost all of the chromosomal imbalances detected with conventional cytogenetic analysis. They are recommended as a first-tier test for postnatal developmental delays, autism spectrum, or with multiple congenital anomalies. Clinically significant findings occur in 15% of those with normal conventional karyotypes.
Specific advantages of microarrays:
- Higher resolution
- Faster turnaround due to automation
- Does not require dividing cells (useful in fetal death)
- Eliminates need to culture amniocytes or chorionic villi
- In a few percent, may detect copy-number variant of uncertain clinical significance
- Increased cost
The referenced study compared chromosomal microarray to karyotyping and enrolled 4406 women at 29 centers who were undergoing prenatal diagnosis. Indications for screening included advanced maternal age (47%), abnormal result on Down’s syndrome screening (19%), structural abnormalities on ultrasonography (25%), and other indications (9%) (some had multiple indications).
The microarrays were of two varieties. The first microarray (71% of cases) consisted of a fourplex array with each array consisting of 44,000 oligonucleotide probes. The second platform (29% of cases) contained 1.8 million oligonucleotide probes.
- Microarray identified all of the abnormalities on conventional karyotyping except for balanced translocations (no loss of genetic material).
- There were 94 of 3822 fetal samples with copy-number variants of uncertain clinical significance (see blog reference below). Subsequently, 30 of these were classified as pathogenic and 8 as benign.
- In samples with normal karyotypes, microarray identified clinically relevant findings in 6% of those with a structural abnormality and 1.7% of those with advanced maternal age or positive Down’s syndrome screening.
The implications of this study and related studies are that microarray has a role in prenatal evaluation of structural abnormalities. Ultimately, whole-exome sequencing will likely supersede microarray analysis and further the conundrum of interpreting abnormalities of uncertain clinical significance.
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