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Two novel splicing mutations in cause TBX5 Holt-Oram syndrome |
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| รหัสดีโอไอ | |
| Creator | Benyanan Phimphakan, Piyobol Kornrat, Thawornchai Limjindaporn, Manop Pithukpakorn, Chanin Limwongse, Natthida Petchampai, Wanna Thongnoppakhun, Chairat Turbpaiboon |
| Title | Two novel splicing mutations in cause TBX5 Holt-Oram syndrome |
| Contributor | Benyanan Phimphakan, Piyobol Kornrat, Thawornchai Limjindaporn, Manop Pithukpakorn, Chanin Limwongse, Natthida Petchampai, Wanna Thongnoppakhun, Chairat Turbpaiboon |
| Publisher | Genetics Society of Thailand |
| Publication Year | 2562 |
| Journal Title | Genomics and Genetics |
| Journal Vol. | 12 |
| Journal No. | 1 |
| Page no. | 1-10 |
| Keyword | TBX5, Holt-Oram syndrome, heart-hand syndrome, congenital heart disease, congenital upper limb anomalies |
| URL Website | https://www.tci-thaijo.org/index.php/gst/issue/view/13960 |
| Website title | https://www.tci-thaijo.org/index.php/gst/article/view/151111 |
| ISSN | 24655198 |
| Abstract | Holt-Oram syndrome (HOS), deformities owing to developmental defects of heart and upper limb, is caused by the TBX5 gene encoding a transcription factor in T-box gene family. Its 1.5-kb coding sequence spans 8 exons for 518 amino acid residues. Most TBX5 mutations are located in the coding region by clustering either in the DNA-binding or in the transactivating domains of TBX5 protein, therefore we investigated 3 Thai (Mongoloid) HOS patients for their causative variants by screening of TBX5 coding sequence. Denaturing high performance liquid chromatography under partial denaturation mode was used to screen for the entire coding region before direct sequencing for specific mutation identification. We report two novel TBX5 mutations (c.983-2A>C, IVS8 as-2 A>C and c.510+5G>A, IVS5 ds+5 G>A as a de novo change) which would affect the splicing process of TBX5 transcript and another recently discovered missense mutation (c.241A>T, p.Arg81Trp) as the first report in Mongoloid HOS patients. Our findings could help extend the understanding of genotype-phenotype correlation in HOS patients which would be beneficial for clinical practice and counseling. |
