| Autor: |
Płatek, Teresa, Sordyl, Maria, Polus, Anna, Olszanecka, Agnieszka, Kroczka, Sławomir, Solnica, Bogdan |
| Zdroj: |
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis; January-June 2023, Vol. 826 Issue: 1 |
| Abstrakt: |
Barth syndrome is a rare disease affecting mitochondria structure and function in males. In our previous study, we have shown a new mutation (c.83T>A, p.Val28Glu) in the TAZgene in two affected patients with congenital cardiomyopathy. Furthermore, women in this family had no mutations in their blood cells, whereas they only had mutations in the oral epithelial cells. The objective of the project was to evaluate the effect of intertissue mosaicisms on the Barth syndrome phenotypes, searching for another disease-related loci on chromosome X and finally to assess the consequences of the mutation. We conducted the advanced genetic study including cytogenetic research (constitutional karyotyping in blood and fibroblasts), NGS sequencing (with custom chromosome X sequencing together with the evaluation of loss of heterozygosity (LOH) and aberrations (CNV) in the whole genome) in four different tissues and sequencing of tafazzin and deoxyribonuclease 1 like 1 transcripts. The presence of deletions within the 5′untranslated region of the TAZgene and/or the noncoding regions of the DNASE1L1gene were detected in several tissues. Whereas, there is no intertissue mosaicism regarding point mutation in TAZgene in all investigated tissues in female carriers. Only the male patient presented biochemical markers and neurological symptoms of Barth syndrome. All the female carriers are healthy and have normal tafazzin and deoxyribonuclease 1 like 1 transcripts in 2 analyzed tissues. The conclusion of this study is that we cannot rule out or confirm mosaicism in the noncoding regions of TAZor DNASE1L1genes, but this is not clinically relevant in female carriers because they are healthy. Finally, it has been proven that mutation (c.83T>A, p.Val28Glu) is responsible for disease in males in this family. |
| Databáze: |
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