ABSTRACT
Objective@#To explore the genetic cause for abnormal pregnancies through detecting chromosomal copy number variations (CNVs) in abortic tissues by next generation sequencing (NGS).@*Methods@#NGS technique was used to detect CNVs in abortion tissues. Parental chromosomal karyotypes were predicted based on the results. The aberrant chromosomal segments of the parents were accurately mapped by G-banding karyotyping analysis and fluorescence in situ hybridization (FISH).@*Results@#In addition to numerical chromosomal aberrations, 12 microdeletion/microduplications were detected by NGS. For 8 families where both parents accepted chromosomal karyotyping, 4 carriers of chromosomal abnormalities were identified. One marker chromosome was missed by karyotyping analysis, and a mother was confirmed to carry a cryptic balanced translocation by FISH.@*Conclusion@#NGS can facilitate detection of cryptic chromosomal translocations in couples with repeated pregnancy failure and is of great value for detecting abnormal CNVs for its high sensitivity.
ABSTRACT
OBJECTIVES: The most common chromosomal abnormality contributing to recurrent abortion is the balanced chromosomal translocation. However the exact incidence of fetal losses are still unknown. The objectives of this study were to evaluate the incidence of fetal chromosomal abnormalities and outcome of pregnancy in recurrent miscarriage couples with balanced translocation. DESIGN: A retrospective analysis of recurrent spontaneous abortion patients with balanced chromosomal translocation. MATERIALS AND METHODS: Cytogenetic analysis was performed in 56 couples with history of recurrent abortions from 1995 to 1999. The use of high resolution banding technique and fluorescent in situ hybridization (FISH) in the chromosomal analysis has made the precise evaluation of chromosome aberrations. RESULTS: Among 56 couples, 42 patients had reciprocal translocation and 14 had Robertsonian translocation. Chromosomal aberrations were more frequent in women (36 cases) than in men (20 cases). Prenatal cytogenetic analyses were carried out in 14 subsequent pregnancies for carrier couples with balanced translocation. The fetal karyotypes showed that 5 cases (35.7%) was normal, 8 (57.1%) were balanced translocation, and 1 (7.1%) was unbalanced translocations. And cytogenetic analyses were done on 15 subsequent chorionic villi samples of abortuses for carrier couples with balanced translocations. Fourteen of fifteen abortuses (93.3%) were abnormal karyotype. CONCLUSIONS: Although the incidence of chromosomal imbalance in the fetuses was relatively low in prenatal cytogenetic analysis, individuals with balanced translocations are predisposed to giving birth to malformed offsprings with chromosomal imbalance (partial trisomy or monosomy). Therefore we recommend preimplantation genetic diagnosis (PGD) for recurrent abortions with balanced translocation and preventing the birth of offspring with chromosomal abnormalities.