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      https://www.ias.ac.in/article/fulltext/jgen/100/0022

    • Keywords

       

      single-sperm sequencing; haplotyping; preimplantation genetic diagnosis; Marfan syndrome; single-nucleotide polymorphism.

    • 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 pre-implantation 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.

    • Author Affiliations

       

      CHUANG LI1 2 FEIFEI ZHOU3 JICHUN TAN3 YAN MAO4 LING YIN KONG4 ZHAO5 YAN ZHANG6 BO LIANG7 JESSE LI LING8 CAIXIA LIU1 2 9 YUAN LYU YUAN LYLYU1 2 9

      1. Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, People’s Republic of China
      2. Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang 110004, People’s Republic of China
      3. Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodelling of Liaoning Province, Shenyang, Liaoning 110022, People’s Republic of China
      4. Basecare Medical Device Co., Ltd., Suzhou 215000, People’s Republic of China
      5. Genetics Unit, Shenyang Maternity and Infant’s Hospital, Shenyang 110004, People’s Republic of China
      6. The Outpatient Department of Obstetrics, Shenyang Maternity and Infant’s Hospital, Shenyang 110004, People’s Republic of China
      7. State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
      8. Jinxin Research Institute of Reproductive Medicine and Genetics, Jinjiang Maternal and Children’s Health Care Hospital, Chengdu 610041, People’s Republic of China
      9. Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Shenyang 110004, People’s Republic of China
    • Dates

       
  • Journal of Genetics | News

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