Confirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Families
| العنوان: | Confirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Families |
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| المؤلفون: | Uluç Yiş, Lena Zeltner, Ahmet Yaramis, Ece Sonmezler, Elmasnur Yilmaz, Ludger Schöls, Rebecca Schüle, Benjamin Bender, Rita Horvath, Ana Töpf, Inga Liepelt, Sofie Kaemereit, Sarah Wiethoff, Stephan Züchner, Benjamin Munro, Steven Laurie, Yavuz Oktay, Semra Hiz, Christoph Kernstock, Hanns Lochmüller, Serdal Güngör |
| المساهمون: | Munro, Benjamin [0000-0003-4506-7092], Horvath, Rita [0000-0002-9841-170X], Apollo - University of Cambridge Repository |
| المصدر: | Journal of Neuromuscular Diseases Journal of neuromuscular diseases 7(3), 301-308 (2020). doi:10.3233/JND-200510 |
| بيانات النشر: | IOS Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Research Report, Adult, Male, Adolescent, Turkey, Mitochondrial disease, Nonsense mutation, Consanguinity, Biology, Frameshift mutation, Mitochondrial Proteins, 03 medical and health sciences, 0302 clinical medicine, medicine, genetics [Leigh Disease], Humans, ddc:610, Leigh disease, Exome sequencing, pathology [Leigh Disease], Genetics, Massive parallel sequencing, physiopathology [Leigh Disease], Haplotype, genetics [Transcription Factors], medicine.disease, 3. Good health, Pedigree, 030104 developmental biology, Neurology, genetics [Mitochondrial Proteins], Female, diagnostic imaging [Leigh Disease], Neurology (clinical), Leigh Disease, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | Background In 2009, we identified TACO1 as a novel mitochondrial disease gene in a single family, however no second family has been described to confirm the role of TACO1 in mitochondrial disease. Objective In this report, we describe two independent consanguineous families carrying pathogenic variants in TACO1, confirming the phenotype. Methods Detailed clinical investigations and whole exome sequencing with haplotype analysis have been performed in several members of the two reported families. Results Clinical phenotype of the patients confirms the originally reported phenotype of a childhood-onset progressive cerebellar and pyramidal syndrome with optic atrophy and learning difficulties. Brain MRI showed periventricular white matter lesions with multiple cystic defects, suggesting leukoencephalopathy in both patients. One patient carried the previously described homozygous TACO1 variant (p.His158ProfsTer8) and haplotype analysis suggested that this variant is a rare founder mutation. The second patient from another family carried a homozygous novel frame shift variant (p.Cys85PhefsTer15). Conclusions The identification of two Turkish families with similar characteristic clinical presentation and an additional homozygous nonsense mutation confirms that TACO1 is a human mitochondrial disease gene. Although most patients with this clinical presentation undergo next generation sequencing analysis, screening for selected founder mutations in the Turkish population based on the precise clinical presentation may reduce time and cost of finding the genetic diagnosis even in the era of massively parallel sequencing. |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| تدمد: | 2214-3602 2214-3599 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::417982beac2ccbd99f6d157e1f298334Test http://europepmc.org/articles/PMC7458500Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....417982beac2ccbd99f6d157e1f298334 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22143602 22143599 |
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