[Prenatal genetic analyses for a woman with a rare cryptic reciprocal insertional balanced translocation]

To explore the genetic characteristics of a rare pedigree with maternal cryptic reciprocal insertional balanced translocation in order to provide genetic counseling and prenatal diagnosis.

A pregnant woman undergoing prenatal diagnosis at Taizhou Hospital on December 19, 2019 and February 7, 2022 and her family members were selected as study subjects. Clinical data of the pedigree were collected. Chromosomal G-banding analysis was performed on the fetus, the couple, and the parents of the pregnant woman. High-throughput genomic copy number variation sequencing (CNV-seq) was also carried out. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K20201009).

The pregnant woman was G₅P₂. Her first pregnancy had delivered by Cesarean section at full-term. The infant had died 10 days after due to hydrocephalus. Her second pregnancy had also delivered by Cesarean section at full-term. The infant underwent resection of congenital megacolon at 6 months of age. At 16 he still showed developmental delay, extremely low intelligence, and language impairment. Her third pregnancy had resulted in spontaneous abortion at 8 weeks of gestation. During her fourth pregnancy, amniotic fluid was collected at 19 weeks for prenatal diagnosis. During her fifth pregnancy, ultrasound revealed mild separation of fetal renal collecting systems, and amniotic fluid was collected at 20 weeks for prenatal diagnosis. The woman's first and second pregnancies were managed by other hospitals, and the result of chromosomal testing was not available. No relevant test was performed upon her third pregnancy. During her fourth pregnancy, analysis of amniotic fluid sample showed a fetal karyotype of 46,U,der(13)ins(13;16)(q31.1;q21q21)mat, and CNV-seq analysis revealed an 8.54 Mb deletion at 13q31.1q31.3 and a 2.88 Mb duplication at 16q21q21. During the fifth pregnancy, analysis of amniotic fluid sample revealed a fetal karyotype of 46,U,der(16)ins(16;13)(q21;q22.2q31.3)mat, and CNV-seq analysis had indicated a 7.8 Mb duplication at 13q22.2q31.1, an 8.54 Mb duplication at 13q31.1q31.3, and a 2.88 Mb deletion at 16q21q21. Analysis of maternal blood sample revealed a karyotype of 46,XX,ins(13;16)(q31.1;q21q21),ins(16;13)(q21;q22.2q31.3), suggested that the woman has carried a cryptic reciprocal insertional balanced translocation, for which the CNV-seq result were normal. The karyotypes and CNV-seq results of her husband and parents were all normal.

The deletion or duplication of 13q31.1q31.3 and 16q21q21 may be the genetic etiology of the adverse pregnancies. The unbalanced gametes may have all resulted from the cryptic reciprocal insertional balanced translocation carried by the woman.