Microarray technology yields greater results in analysis of genetic abnormalities in stillbirths compared to karyotyping, largely because of the ability to analyze nonviable tissue. The improved yield can detect greater numbers of aneuploids and is more sensitive to the presence of additional pathogenic variants, according to a study published in the Dec. 6 issue of the New England Journal of Medicine. The researchers from the Stillbirth Collaborative Research Network analyzed data from 532 stillbirth samples obtained from 59 different hospitals. A single-nucleotide polymorphism array (Affymetrix GenomeWide Human SNP Array 6.0) was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. The microarray analysis was conducted at a single university medical center, while the karyotype analysis was conducted in multiple university-affiliated laboratories. Microarray analysis yielded significantly more results than karyotyping (87.4 percent versus 70.5 percent) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants) than karyotyping (8.3 percent versus 5.8 percent). Microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9 percent in all stillbirths, 34.5 percent in antepartum stillbirths, and 53.8 percent in stillbirths with anomalies, compared with karyotyping. “Microarray analysis is more likely than karyotype analysis […]
Microarray technology yields greater results in analysis of genetic abnormalities in stillbirths compared to karyotyping, largely because of the ability to analyze nonviable tissue. The improved yield can detect greater numbers of aneuploids and is more sensitive to the presence of additional pathogenic variants, according to a study published in the Dec. 6 issue of the New England Journal of Medicine.
The researchers from the Stillbirth Collaborative Research Network analyzed data from 532 stillbirth samples obtained from 59 different hospitals. A single-nucleotide polymorphism array (Affymetrix GenomeWide Human SNP Array 6.0) was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. The microarray analysis was conducted at a single university medical center, while the karyotype analysis was conducted in multiple university-affiliated laboratories.
Microarray analysis yielded significantly more results than karyotyping (87.4 percent versus 70.5 percent) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants) than karyotyping (8.3 percent versus 5.8 percent). Microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9 percent in all stillbirths, 34.5 percent in antepartum stillbirths, and 53.8 percent in stillbirths with anomalies, compared with karyotyping.
“Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained,” say the authors, led by Uma M. Reddy, M.D., from the National Institutes of Health in Bethesda, Md.
Variants detected that were not identified in three reference databases were classified into three groups: probably benign, clinical significance unknown, or pathogenic. Some of the pathogenic variants that were detected on microarray analysis may represent unbalanced translocations, which can be missed by karyotyping.
Only microarray analysis detected three copy-number variants in three stillbirths at chromosome 22q11.2, a region disrupted in the DiGeorge syndrome. A recurrent variant of unknown significance in a telomeric region of chromosome 19p13.3 (ranging in size from 632 kb to 930 kb) was seen in eight stillbirths, a region known to contain multiple benign variants as well as five loci associated with disease, but not with stillbirth or developmental disorders.
When factoring variants of unknown significance into the comparison of karyotyping versus microarray technology, there was an even greater significant detection of abnormalities with microarray technology (13 percent versus 5.8 percent). Of the 157 stillbirths for which karyotyping failed to yield a definitive result, 79.6 percent yielded a definitive microarray result, of which 5.7 percent were abnormal.
