OBJECTIVETo use next generation sequencing (NGS) to identify unknown abnormality of chromosome 9 in a fetus and explore its mechanism.

METHODSA pregnant woman with abnormal fetal ultrasound finding underwent amniocentesis for G-banded chromosomal analysis. Karyotyping was also performed on peripheral blood samples derived from its parents. Fetal blood sample was obtained for NGS testing to identify abnormality unrecognized by karyotyping.

RESULTSAnalysis of amniocytes has revealed a 46,XX,der(9)(?::p21 to qter) karyotype, while both parents had a normal karyotype. NGS analysis of the fetus revealed a 20.67 Mb duplication (4 454 279-25 126 275) at 9p21.3p24.2, which overlapped with that of the 9p duplication syndrome, and a 4.43 Mb deletion at 9p24.2p24.3 (10 001-4 442 364), which partially overlapped with that of 9p deletion syndrome and 46,XY sex reversal 4 region. Comparison of the sequencing data with reference genome database indicated direct duplication of 9p21.3p24.2, which was also supported by review of the morphology of chromosome 9p. Therefore, the karyotype of the fetus was verified to be 46,XX,der(9) dir dup(9)(p21.3p24.2), del(9)(p24.2p24.3).

CONCLUSIONCombined G-banded karyotyping and NGS can identify dir dup del(9p) with accuracy. Delineation of the mechanism of dir dup del(9p) and its genotype-phenotype correlation may facilitate genetic counseling and estimation of recurrence risk.