Study finds new mutation in child after embryo screening
image: C-MoKa detection of translocation breakpoints. (A) Inherited der(13;14) breakpoint in the male patient; (B) de novo breakpoint in the offspring with a stronger interaction signal (red arrow).
Credit: Wang, Zhi-Qiang; Yang, Lin-Yan; Yan, Bo; Yang, Jin-Wei; Xiong, Yue; Wang, Cheng; Zhang, Chuan; Ni, Ya-Li.
A couple who underwent embryo screening to avoid passing a chromosomal condition to their child received an unexpected prenatal diagnosis: their child carried the same condition as the father. An investigation found that the child's condition was a new mutation, not an inherited one.
The report, published in Reproductive and Developmental Medicine, describes the case of a 28-year-old male with a Robertsonian translocation der(13;14)(q10;q10), a fusion of chromosomes 13 and 14 that can cause infertility or miscarriage. The couple underwent preimplantation genetic testing (PGT-SR) to select an embryo that did not carry the father's translocation.
However, prenatal diagnosis at 20 weeks of gestation revealed that the fetus carried the same Robertsonian translocation present in the father.
"We were initially surprised by the result because the embryo had been tested and confirmed not to carry the father's translocation," said Dr. Ni Ya-Li from Gansu Provincial Maternity and Child-Care Hospital, China. "This prompted us to conduct a thorough investigation to understand what had happened."
The research team then ran several checks to find out how this occurred.
The team first ruled out lab errors or sample mix-ups. DNA comparison confirmed the child came from the intended embryo. Next, they examined the fused chromosomes from both father and child and found they were different, meaning the child did not inherit the condition directly.
Finally, the team used a newer method called C-MoKa. This method showed that the location where the two chromosomes fused was different in the child compared to the father. The child's fusion was a new event. Further testing confirmed that the child's fused chromosome came from normal chromosomes from both parents, not from the father's fused copy.
The study concludes that the child's Robertsonian translocation was a de novo mutation, meaning it arose newly during the formation of reproductive cells or early embryonic development.
"This case shows that even with the most careful embryo screening, we cannot assume that every potential genetic risk has been eliminated," said Dr. Ni.
The authors note that PGT-SR remains effective for known abnormalities but cannot detect new translocations that may arise. They recommend that prenatal diagnosis should still be offered after PGT-SR.
According to the authors, this is the first time a de novo isovariant event within a Robertsonian translocation has been validated using multiple techniques, providing valuable evidence for genetic counseling before PGT-SR.