Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome.

Case Report: A 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+21[12]/48,XX,+21,+mar[3]. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+21[37]/48,XX,+21,+mar[3]. The umbilical cord had a karyotype of 47,XX,+21[38]/48,XX,+21,+mar[2]. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40∼50% mosaicism for a 2.604-Mb duplication of 15q25.2-q25.3, or arr 15q25.2q25.3 (83,229,665-85,834,131) × 2.4 [GRCh37 (hg19)] encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21.

Conclusion: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.