Both types of platforms detect aneuploidy, unbalanced translocations, and microdeletions and microduplications. Neither type of array platform currently detects balanced chromosomal rearrangements. For this reason, couples with recurrent pregnancy loss should be ofered karyotyping as the first-line test (Society for Maternal-Fetal Medicine, 2016). In addition, SNP arrays are able to identiY triploidy and can detect absence of heterozygosiy. he latter can occur with uniparental disomy when both copies of a chromosome are inherited from one parent. Further, absence of heterozygosity may occur when there is consanguinity, and counseling prior to performance of an SNP array should include this possibility.
Arrays may be genome-wide or may be targeted to known genetic syndromes. Genome-wide arrays are typically used in research settings, for example, to identiY novel microdeletion syndromes in individuals with intellectual disability (Slavotinek, 200S). Targeted arrays are generally preferred prenatally because the likelihood of detecting a copy number variant of uncertain clinical signiicance is lower. In a systematic 1.28 cm
A Actual size of chip
Nonhybridized Thousands of identical nucleotide DNA strands on one cell
B 500,000 cells on each chip
C One cell on chip Labeled fetal DNA is presented to the cells
FIGURE 13-13 Chromosomal microarray analysis. A. Actual microarray chip size. B. Each chip contains thousands of cells (squares). C & D. Each cell contains thousands of identical oligonucleotides on its surface, and each cell is unique in its nucleotide content. E. During genetic analysis, a mixture containing tagged fetal DNA is presented to the chip. Complementary DNA sequences bind. F. If a laser is shined on the chip, DNA sequences that have bound will glow. This identifies a matching sequence. (Modified with permission from Doody J: Treatment of the infertile couple. In Hofman BL, Schorge JO, Schaffer JI, et al (eds): Williams Gynecology, 2nd ed. New York, McGraw-Hili, 2012.) review, Hillman and colleagues (2013) identified copy number variants of uncertain significance in 1 to 2 percent of prenatal specimens. Not unexpectedly, this may be a source of signiicant distress to families, even with comprehensive pretest counseling.
In pregnancies at increased risk for autosomal trisomy based on aneuploidy screening, karyotyping or FISH plus karyotyping should be ofered, and CMA should be made available (American College of Obstetricians and Gynecologists, 2016b). When the karyotype is normal, CMA has identiied clinically relevant copy number variants in approximately 6.5 percent of pregnancies with fetal abnormalities and in 1 to 2 percent with no obvious fetal abnormality (Callaway, 2013). he American College of Obstetricians and Gynecologists (2016b) and the Society for Maternal-Fetal Medicine (2016) recommend that CMA be ofered as a irst-tier test when fetal structural abnormalities are identiied, replacing fetal karyotyping in these cases. If a particular anomaly that strongly suggests a speciic aneuploidy is identiied, such as an endocardial cushion defect (trisomy 21) or alobar holoprosencephaly (trisomy 13), karyotyping or FISH may be ofered as the initial test. It is recommended that genetic counseling include information about the beneits and limitations of both CMA and karyotyping, and that each be made available to women who elect prenatal diagnosis (Society for Maternal-Fetal Medicine, 2016). CMA may identiy instances of autosomal dominant genetic disorders that have not yet manifested in an afected parent, and it may also identiy instances of nonpaternity.