Abstract
Marfan syndrome (MFS) is caused by a FBN1 mutation. Many organ systems are affected in patients with MFS, including the skeletal, ocular, cardiovascular and pulmonary systems. Cardiovascular manifestations are the main cause of mortality in patients with MFS. The mode of inheritance of MFS is autosomal dominant inheritance and the offspring are at great risk for the disease. Thus, the genetic testing for monogenic disease during preimplantation (PGT-M) is routinely advised for patients with MFS. PGT-M is a clinical genetic method to obtain normal embryos which are not affected by the monogenetic disorder. However, allele drop out (ADO) typically results in misdiagnosis during the PGT-M in the autosomal dominant disorder. Thus, a linkage analysis of polymorphic sites is used to identify ADO and improve the accuracy of PGT-M. However, when there are no family members affected, or the patients carry a de novo mutation, a linkage analysis cannot be performed to position the abnormal chromatid. Here, we performed single-sperm sequencing of preimplantation genetic testing in a male patient with MFS with a de novo mutation in FBN1. We constructed the chromosomal haplotype of the male patient by analysing information at the mutation site and at polymorphic sites. Next, the normal embryos were selected based on the results of high-throughput sequencing and haplotyping, and the one frozen embryo was transferred to the uterus. Finally, the preimplantation genetic testing results were confirmed by the prenatal genetic diagnosis during pregnancy, which showed that the foetus did not carry the pathogenic mutation. In conclusion, our research showed that single-sperm sequencing and haplotype analysis can be used in male patients with monogenetic disorders caused by de novo mutations to improve the accuracy of the preimplantation genetic diagnosis.
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Acknowledgements
We thank the family who participated in this study. This study was jointly supported by the Natural Science Foundation of China (no. 81701462) and National Key Research Programme (2018YFC1002900).
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Li, C., Zhou, F., Tan, J. et al. Application of single-sperm sequencing in a male with Marfan syndrome: a case report and a literature review. J Genet 100, 22 (2021). https://doi.org/10.1007/s12041-021-01267-5
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DOI: https://doi.org/10.1007/s12041-021-01267-5