Chromosomal microarray analysis of 339 fetuses with increased nuchal translucency and normal karyotype / 中华围产医学杂志

ABSTRACT

Objective To explore the value of chromosome microarray analysis (CMA) in determining the genetic etiology of fetuses with increased nuchal translucency (NT) but normal karyotype. Methods Amniocentesis, karyotype analysis and CMA were performed to singleton pregnant women with increased fetal NT ( ≥ 3.0 mm) in early pregnancy (11+1-13+6 gestational weeks) at Shenzhen Maternity and Child Healthcare Hospital from March 2015 to December 2017. A total of 339 fetuses with normal G banding karyotype analysis were recruited retrospectively. Peripheral blood samples were collected for CMA in parents whose fetuses were detected with pathogenic copy number variations (CNVs) or variants of uncertain significance (VUS). Descriptive analysis was used for CMA results. Moreover, Pregnancy outcomes and postnatal conditions of fetuses with abnormal CNVs were followed up. Results Pathogenic CNVs, ranging from 68 kb to 12.636 Mb, were detected in 15 out of the 339 fetuses (4.4%) including four microduplications and 11 microdeletions. Among them, there were eight known microdeletion or microduplication syndromes (nine cases) including Williams-Beuren syndrome, 18p deletion syndrome,Wolf-Hirschhorn syndrome, 22q11 duplication syndrome, 16p11.2 deletion syndrome, 17p13.3 duplication syndrome, 16p11.2 duplication syndrome (one case respectively) and DiGeorge syndrome/velocardiofacial syndrome (two cases). Of the 11 fetuses with VUS, five cases originated from parents with normal phenotype and the identified VUS were benign and the rest six were de novo mutations[1.8%(6/339)]. Of the 15 fetuses with pathogenic CNVs, one was lost to follow-up, four were live born and two of which was found to be growth retardation at the age of two. Among the 11 fetuses with VUS, nine were live born and no abnormality was reported in any cases at one year old. Conclusions For fetus with increased NT and normal karyotype, CMA is able to identify chromosomal microdeletion/microduplication that are not recognized by conventional karyotyping analysis, and may play an important role in prenatal diagnosis and genetic counseling.