Open AccessNext‐generation sequence‐based preimplantation genetic testing for monogenic disease resulting from maternal mosaicism
Author(s) -
Hu Xiao,
He WenBin,
Zhang ShuoPing,
Luo KeLi,
Gong Fei,
Dai Jing,
Zhang Yi,
Wan ZhenXing,
Li Wen,
Yuan ShiMin,
Tan YueQiu,
Lu GuangXiu,
Lin Ge,
Du Juan
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1662
Subject(s) - genetics , genetic testing , disease , biology , sequence (biology) , computational biology , preimplantation genetic diagnosis , dna sequencing , medicine , pregnancy , gene , pathology
Background Mosaicism poses challenges for genetic counseling and preimplantation genetic testing for monogenic disorders (PGT‐M). NGS‐based PGT‐M has been extensively used to prevent the transmission of monogenic defects, but it has not been evaluated in the application of PGT‐M resulting from mosaicism. Methods Four women suspected of mosaicism were confirmed by ultra‐deep sequencing. Blastocyst trophectoderm cells and polar bodies were collected for whole genome amplification, followed by pathogenic variants detection and haplotype analysis based on NGS. The embryos free of the monogenic disorders were transplantable. Results Ultra‐deep sequencing confirmed that the four women harbored somatic mosaic variants, with the proportion of variant cells at 1.12%, 9.0%, 27.60%, and 91.03%, respectively. A total of 25 blastocysts were biopsied and detected during four PGT cycles and 5 polar bodies were involved in one cycle additionally. For each couple, a wild‐type embryo was successfully transplanted and confirmed by prenatal diagnosis, resulting in the birth of four healthy infants. Conclusions Mosaic variants could be effectively evaluated via ultra‐deep sequencing, and could be prevented the transmission by PGT. Our work suggested that an NGS‐based PGT approach, involving pathogenic variants detection combined with haplotype analysis, is crucial for accurate PGT‐M with mosaicism.