SNP Microarray for Prenatal Test

【Abstract】
In this volume we will share the internal GGA data on SNP Array for Prenatal Test with focuses on comparisons of fetal and parental results, the importance of parental follow-up testing and how it may change provider-patient genetic counseling discussion as well as risk assessment for the fetus.

In this current analysis:
– Nearly 7,000 results from SNP Array for Prenatal Test were analyzed
– The rate of abnormality within this population was 4.9%
– About two-thirds of the abnormal results were genetic changes that cannot be detected by routine chromosome analysis (karyotype)

The importance of parental follow-up SNP array testing can be clearly seen when a fetus is found to carry a genetic change of unclear clinical significance. Determination of whether a genetic change in the fetus is inherited or not can help delineate the clinical significance of this change
and help reduce parental anxiety. This helps to provide more information for discussion between the providers and the patients, and prevent potential irreversible action on the pregnancy due to insufficient information.

In this current analysis:
– Parental follow-up SNP array testing was recommended for 180 fetal results.
– Over 300 parental follow-up SNP array results were analyzed.
– In cases with known parental information, about 80% of the fetal genetic changes identified were familial.
– Of the hereditary cases, about half was inherited from the mother and half from the father.

The spectrum of clinical information provided by knowledge of parental status differs based on the type and the pathogenicity nature of the genetic change identified in the fetus.

Here we present our internal findings in regards to a few commonly encountered scenarios in which parental follow-up SNP array test would be recommended. Counseling notes for each scenario are also provided.

【GGA Experience】
Of the close to 7,000 SNP Array for Prenatal Test results, the proportions of abnormal results are as follows:

About 3.3% of these prenatal samples showed copy number variations (CNV)-microduplications/microdeletions, or loss of heterozygosity (LOH)-risk for uniparental disomy (UPD) disorders. These are genetic changes not typically detectable with routine chromosome analysis. In other words, for these patients, if SNP Array was not prenatally pursued, it is very likely that the child would not been found to have a severe genetic condition until concerning symptoms develop monthly or years after birth. This illustrates the importance and the benefit of prenatal testing with SNP array.

Subsequent comparison with parental follow-up SNP array was recommended for 180 fetal results to better delineate the clinical significance of the fetal genetic change discovered. This can help reduce potential uncertainties regarding the fetus. This piece of knowledge also provides medical staff and the family additional information for discussion in regards to pregnancy plans.

With the SNP array platform and GGA internal analytical standard and reporting criteria for prenatal arrays, some commonly encountered scenarios in which parental follow-up testing is recommended are as follows:

A. Likely benign or Variant of uncertain clinical significance (VOUS) CNV:
 A chromosomal change in which the clinical significance is currently uncertain
 Available literature support and evidence is limited
 Can potentially be benign in nature

B. Likely pathogenic CNV:
 A chromosomal change in which there are scientific literature and database to suggest association with abnormal clinical presentations.
 The change has also been reported in clinically normal individuals.

C. Loss of heterozygosity / Increased risk for uniparental disomy:
 A chromosomal change in which allelic genotypes reveals LOH in large chromosomal segments.
 This can be non-pathogenic or may be related to UPD disorders with risk for clinical abnormality.

The following are individual discussions of each type of the genetic changes:

There are still much to learn in the world of genetics. Not all chromosomal changes have sufficient information to determine their clinical implication with currently available medical and scientific knowledge. When encountering genetic changes with undetermined clinical significance, parental follow-up SNP array comparisons can help further delineate the clinical significance and the risk to the fetus. In some cases, the results of the parental analyses not only help further assess the level of risk to the fetus, but also help understand more about individual familial characteristics and potential reproductive risks for other family members. This information may help lower parental anxiety and concerns, allow providers and patients to have a more comprehensive counseling discussion, and potentially prevent irreversible pregnancy action made because of the lack of information.

The accumulation of fetal SNP array data and parental results will also allow us to gain knowledge and better understand our own population-specific characteristics for the people in Taiwan. This may serve as a valuable resource for case consultations in the future.