Elsevier

Genetics in Medicine

Volume 20, Issue 1, January 2018, Pages 128-131
Genetics in Medicine

Original Research Article
When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations

https://doi.org/10.1038/gim.2017.89Get rights and content
Under an Elsevier user license
open archive

Abstract

Purpose

To compare the frequency of copy-number variants (CNVs) of variable penetrance in low-risk and high-risk prenatal samples and postnatal samples.

Methods

Two cohorts were categorized according to chromosomal microarray analysis (CMA) indication: group I, low-risk prenatal—women with uneventful pregnancy (control group); group II, high-risk prenatal—women whose fetuses had congenital malformations; and group III, postnatal—individuals with unexplained developmental delay/intellectual disability, autism spectrum disorders, or multiple congenital anomalies. CNVs were categorized based on clinical penetrance: (i) high (>40%), (ii) moderate (10–40%), and (iii) low (<10%).

Results

From 2013 to 2016, 21,594 CMAs were performed. The frequency of high-penetrance CNVs was 0.1% (21/15,215) in group I, 0.9% (26/2,791) in group II, and 2.6% (92/3,588) in group III. Moderate-penetrance CNV frequency was 0.3% (47/15,215), 0.6% (19/2,791), and 1.2% (46/3,588), respectively. These differences were statistically significant. The frequency of low-penetrance CNVs was not significantly different among groups: 0.6% (85/15,215), 0.9% (25/2,791), and 1.0% (35/3,588), respectively.

Conclusion

High-penetrance CNVs might be a major factor in the overall heritability of developmental, intellectual, and structural anomalies. Low-penetrance CNV alone does not seem to contribute to these anomalies. These data may assist pre- and posttest CMA counseling.

Keywords

chromosomal microarray analysis (CMA)
copy-number variation (CNV)
penetrance
prenatal diagnosis

Cited by (0)