Clinical and Molecular Features of 5 European Multigenerational Families With Moyamoya Angiopathy
| العنوان: | Clinical and Molecular Features of 5 European Multigenerational Families With Moyamoya Angiopathy |
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| المؤلفون: | Dominique Vidaud, Florence Riant, Lou Grangeon, Chaker Aloui, Françoise Bergametti, Jan Claudius Schwitalla, Markus Kraemer, Jessica Hadjadj, Stéphanie Guey, Severine Drunat, Minh Arnould, Michaelle Corpechot, Elisabeth Tournier-Lasserve |
| المصدر: | Stroke. 50:789-796 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Proband, Adolescent, Ubiquitin-Protein Ligases, Angiopathy, Young Adult, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Gene Frequency, Exome Sequencing, Phosphoprotein Phosphatases, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, Moyamoya disease, Age of Onset, Child, Gene, Alleles, Genetic Association Studies, Exome sequencing, Aged, 030304 developmental biology, Adenosine Triphosphatases, Advanced and Specialized Nursing, Genetics, 0303 health sciences, business.industry, Livedo racemosa, Middle Aged, medicine.disease, Pedigree, Europe, Mutation, Mendelian inheritance, symbols, Female, Neurology (clinical), Moyamoya Disease, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery |
| الوصف: | Background and Purpose Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy outside of Asia. In Japanese patients, a vast majority of patients carry the founder p.R4810K variant in the RNF213 gene, and familial cases are around 10%. In European patients, data about familial occurrence are limited. The aim of this study was to characterize the clinical and molecular features of several European families with a parent-to-child transmission of MMA. Methods Out of 126 MMA probands referred, we identified 113 sporadic probands and 13 familial probands. Segregation analysis showed a vertical parent-to-child pattern of inheritance in the families of 5 of these probands. All 5 families were of German or Dutch ancestry. We investigated the clinical features of affected members and used whole-exome sequencing to screen RNF213 and 13 genes involved in Mendelian MMA and to identify genes recurrently mutated in these families. Results Twelve affected MMA patients were identified, including 9 females and 3 males. Age at clinical onset ranged from 11 to 65 years. In 3 of 5 families, associated livedo racemosa was found. We did not detect any deleterious variants in the 13 known MMA genes. RNF213 rare missense variants predicted to be pathogenic were detected in all affected members of 2 of these families, as well as 2 candidate variants of the PALD1 gene. Conclusions Nonsyndromic MMA was identified in 5 European families, including 2 to 3 clinically affected cases segregating with a parent-to-child pattern of inheritance in each family. Molecular screening detected rare deleterious variants within RNF213 and PALD1 in all affected members of 2 of these 5 families, as well as in some clinically unaffected members. Altogether these data raise the difficult and, to date unanswered, question of the medical indication of presymptomatic screening. |
| تدمد: | 1524-4628 0039-2499 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc2b6c2c56ec702ec0fbfe4b310b1f15Test https://doi.org/10.1161/strokeaha.118.023972Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc2b6c2c56ec702ec0fbfe4b310b1f15 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244628 00392499 |
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