A novel TBX1 missense mutation in patients with syndromic congenital heart defects
| Autor: | Samir Kamoun, Chahnez Triki, Mohamed Ali Ksentini, Neila Belghuith, Fatma Abdelhedi, Hassen Kamoun, Mongia Hachicha, Imen Chabchoub, Fatma Kamoun, Mouna Tabebi, Sirine Maatoug, Hajer Doukali, Amel Jaouadi, Dorra Abid, Leila Keskes |
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| Rok vydání: | 2018 |
| Předmět: |
Heart Defects
Congenital Models Molecular 0301 basic medicine TBX1 Candidate gene Chromosomes Human Pair 22 DNA Mutational Analysis Mutation Missense Biophysics Locus (genetics) Single-nucleotide polymorphism 030204 cardiovascular system & hematology Biology Biochemistry 03 medical and health sciences 0302 clinical medicine medicine Humans Missense mutation Computer Simulation Amino Acid Sequence Molecular Biology Gene In Situ Hybridization Fluorescence Genetics Base Sequence medicine.diagnostic_test Syndrome Cell Biology Phenotype 030104 developmental biology Karyotyping T-Box Domain Proteins Fluorescence in situ hybridization |
| Zdroj: | Biochemical and Biophysical Research Communications. 499:563-569 |
| ISSN: | 0006-291X |
| Popis: | Congenital heart defects represent a characteristic part of several genetic syndromes associated with chromosomal abnormalities such as 22q11.2 deletion syndrome; many genes located in this locus, mainly TBX1, are candidate genes for congenital heart defects. In our cohort of 27 subjects with congenital heart defect, both karyotype analysis and Fluorescence in situ hybridization (FISH) were performed. The TBX1 gene was sequenced in patients lacking chromosomal abnormalities. FISH analysis showed a de novo 22q11.2 deletion in two patients. The screening of TBX1 coding sequence identified a novel missense mutation c.569C > A (p.P190Q) in six unrelated patients and detected two associated known single nucleotide polymorphisms; the c.664C > T (rs2301558) in three patients and the c.420T > C (p.Phe140 Phe) (rs41298814) in one patient. Bioinformatic tools show that the novel missense mutation c.569C > A could modify the function and the stability of the TBX1 protein. The c.569C > A mutation was not found in 50 healthy controls. Ours results suggest a deleterious role of the c.569C > A mutation and strengthen the hypothesis that this mutation might be responsible for the same phenotype spectrum as the 22q11.2 deletion syndrome. |
| Databáze: | OpenAIRE |
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