OBJECTIVETo explore the genetic etiology for fetuses with increased nuchal translucency (NT) but a normal karyotype at whole genome level by chromosome microarray analysis (CMA).

METHODSSeventy-eight fetuses with increased NT (≥ 3.0 mm) but a normal karyotype were collected between 11(+0) and 13(+6) gestational weeks. Genomic DNA was extracted, and microarray testing was performed using Affymetrix CytoScan(TM) HD arrays. The data was analyzed by CHAS software. All detected copy number variations (CNVs) were confirmed with real-time quantitative polymerase chain reaction.

RESULTSThe CMA assay has detected pathogenic CNVs in 6 fetuses (7.69%), which have ranged from 0.41 Mb to 15.87 Mb. Well-known microdeletion or microduplication syndromes including Wolf-Hirschhorn syndrome, 22q11 microdeletion syndrome and ATR-16 syndrome were identified in three cases. The detection rates in fetuses with or without structural abnormalities were 18.18% and 5.97%, respectively (P=0.198 with Fisher's Exact Test). The average NT in fetuses with pathogenic CNVs and non-pathogenic CNVs has measured 4.48 mm and 4.22 mm (P=0.735 by Mann-Whitney Test).

CONCLUSIONFor fetuses with increased NT, CMA can identify chromosomal microdeletion/microduplication unrecognizable by conventional karyotyping analysis. It may therefore play an important role in prenatal diagnosis and genetic counseling by improving the diagnostic rate.