Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

Hongyan Chai,Peining Li,Jennifer Boyle,Autumn DiAdamo,Dongmei Wang,Katherine Amato,Brittany Grommisch,Jiadi Wen

doi:10.3390/medsci7020016

Abstract

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements, and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested an under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.

Highlights

Major chromosomal abnormalities have been detected in 0.65% of newborns from combined surveys during 1969–1982; and approximately 75% of these chromosomal abnormalities are common aneuploidies involving chromosomes 13, 18, 21, X, and Y [1]
Since the 1980s, prenatal diagnosis of pregnancies at risk of common aneuploidies have been indicated by abnormal maternal serum screening, advanced maternal age, abnormal ultrasound findings on the fetus, and family history of chromosome abnormalities
Changes in and efficacies of indications for invasive prenatal diagnosis have been noted, especially with the introduction of a highly effective screening of common aneuploidies by non-invasive prenatal testing (NIPT) using next-generation sequencing on maternal serum cell free fetal DNA [6,7,8]

Summary

Introduction

Major chromosomal abnormalities have been detected in 0.65% of newborns from combined surveys during 1969–1982; and approximately 75% of these chromosomal abnormalities are common aneuploidies involving chromosomes 13, 18, 21, X, and Y [1]. Changes in and efficacies of indications for invasive prenatal diagnosis have been noted, especially with the introduction of a highly effective screening of common aneuploidies by non-invasive prenatal testing (NIPT) using next-generation sequencing on maternal serum cell free fetal DNA [6,7,8]. Despite all these technical advancements, correlating cell-based FISH and chromosome results to resolve pseudo-mosaicism by culture artifact, fetoplacental discrepancy by confined placental mosaicism (CPM), and true fetal mosaicism (TFM) is still a major challenge in both laboratory operation and result interpretation [9,10,11]

Methods

Results

Discussion

Conclusion