Chromosomal microarray analysis of 85 fetus with growth restriction

Abstract

Objective To investigate the clinical value of chromosomal microarray analysis (CMA) in identifying the genetic etiology of fetal growth restriction (FGR). Methods Eighty-five FGR cases were recruited from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2014 to October 2016. Samples of amniotic fluid (n=74), skin tissues from aborted fetuses (n=9), umbilical cord blood (n=1) and peripheral blood from a premature infant (n=1) were collected. Affymetrix CytoScan 750K Array was used to detect copy number variation (CNV) in fetal samples. Microarray analysis or fluorescence quantitative polymerase chain reaction was further recommended for the parents if fetal CMA result was variants of unknown significance (VOUS). Karyotype analysis of umbilical cord blood was further recommended if fetal CMA result was chromosome mosaicism. Chromosome analysis of peripheral blood was further recommended for the parents if fetal CMA result of a fetus was submicroscopic CNVs. Adjusted Chi-square test was used as the statistical method. Results CMA was successful in all samples in identifying chromosomal abnormalities. Among the 36 isolated FGR cases (42.4%, 36/85), CMA identified in four cases of chromosome imbalance recombination and four cases of VOUS, and the rest 28 cases were normal. Besides, no CNV was detected. Among the other 49 FGR cases (57.6%, 49/85) with ultrasound abnormalities, there were five cases of VOUS, and five cases of chromosome imbalance recombination and nine cases of CNVs. No significance difference in the detection rate of chromosome imbalance recombination was observed between the isolated and non-isolated FGR groups [11% (4/36) vs 10% (5/49), adjusted χ2=0.000, P>0.999]. Parents of six cases of VOUS were further examined and the same variants was found in either one. One case of sex chromosome mosaicism was validated by cord blood karyotyping. One case of chromosome imbalance recombination was due to the paternal balanced translocation. Conclusions CMA is helpful in detecting the chromosome imbalance recombination in FGR cases. Key words: Fetal growth retardation; Microarray analysis; Chromosomes, human; DNA copy number variations