دورية أكاديمية
RFC1 nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology.
| العنوان: | RFC1 nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology. |
|---|---|
| المؤلفون: | Benkirane, Mehdi, da Cunha, Dylan, Marelli, Cecilia, Larrieu, Lise, Renaud, Mathilde, Varilh, Jessica, Pointaux, Morgane, Baux, David, Ardouin, Olivier, Vangoethem, Charles, Taulan, Magali, Daumas Duport, Benjamin, Bergougnoux, Anne, Corbillé, Anne Gaelle, Cossée, Mireille, Juntas Morales, Raul, Tuffery-Giraud, Sylvie, Koenig, Michel, Isidor, Bertrand, Vincent, Marie Claire |
| المساهمون: | Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Recherche Clinique (IURC Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) |
| المصدر: | ISSN: 0006-8950. |
| بيانات النشر: | HAL CCSD Oxford University Press |
| سنة النشر: | 2022 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive. We screened by clinical exome sequencing two unrelated patients presenting with late onset ataxia. Repeat Primer-PCR was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription PCR We identified the first two CANVAS affected patient who are compound heterozygous for a RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to 3 patients with bi-allelic RFC1 expansions. In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss of function as the cause of the disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03750598; https://hal.science/hal-03750598Test; https://hal.science/hal-03750598/documentTest; https://hal.science/hal-03750598/file/2022%20Benkirane%20et%20al.,%20RFC1%20nonsense.pdfTest |
| DOI: | 10.1093/brain/awac280 |
| الإتاحة: | https://doi.org/10.1093/brain/awac280Test https://hal.science/hal-03750598Test https://hal.science/hal-03750598/documentTest https://hal.science/hal-03750598/file/2022%20Benkirane%20et%20al.,%20RFC1%20nonsense.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3FA1D78E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awac280 |
|---|