دورية
RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders
| العنوان: | RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders |
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| المؤلفون: | He, Wen-Bin, Xiao, Wen-Juan, Dai, Cong-Ling, Wang, Yu-Rong, Li, Xiu-Rong, Gong, Fei, Meng, Lan-Lan, Tan, Chen, Zeng, Si-Cong, Lu, Guang-Xiu, Lin, Ge, Tan, Yue-Qiu, Hu, Hao, Du, Juan |
| المصدر: | Journal of Medical Genetics (JMG); 2022, Vol. 59 Issue: 10 p1010-1016, 7p |
| مستخلص: | BackgroundNumerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable.ObjectiveTo assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning.MethodsForty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT).ResultsEleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up.ConclusionRNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2021-108013 |