Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum
| العنوان: | Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum |
|---|---|
| المؤلفون: | Calvin Soh, Sophie Calvert, Ram L. Kumar, Isabelle Desguerre, Kevin Talbot, Evangeline Wassmer, Axel Panzer, Andrea Berger, Anna de Burca, Anu Jacob, Andrea Whitney, Andrew P. Badrock, Frances Gibbon, Shelley MacDonald, Rhys H. Thomas, Reza Maroofian, Heather Burnett, Elizabeth Jones, Thomas Blauwblomme, Francois V. Bolduc, Jamal Ghoumid, Mickaël Ferrand, Yanick J. Crow, Emma M. Jenkinson, Camilo Toro, Diana Chiang, Roseline Caumes, Gillian I. Rice, Gemma Fisher, Gopinath M. Subramanian, Edoardo Monfrini, Renaud Touraine, Hilde T. Hilmarsen, Sarju G. Mehta, Imelda Hughes, Sumit Parikh, Edward Blair, Mary O'Driscoll, Sarah Dyack, Himanshu Goel, Kristin W. Barañano, Prab Prabhakar, Luis Seabra, Roberta Battini, John H. Livingston, Russell P. Saneto, Richard J. Leventer, Katrin Õunap, Heather Marshall, Andy Cheuk Him Ng, Duccio Maria Cordelli, Natasha Demic, Daniela Neumann, Natalie Boddaert, Michael J. Noetzel, S. Richard Dunham, Ehsan Ghayoor Karimiani, Johannes A. Buckard, Frances Elmslie, Raymond T. O'Keefe, Chloe A Stutterd, Richard Sandford, Imke Metz, Francis Ramond, Liesbeth De Waele, Alessio Di Fonzo, Emma Wakeling, David B. Clifford |
| المساهمون: | Crow Y.J., Marshall H., Rice G.I., Seabra L., Jenkinson E.M., Baranano K., Battini R., Berger A., Blair E., Blauwblomme T., Bolduc F., Boddaert N., Buckard J., Burnett H., Calvert S., Caumes R., Ng A.C.-H., Chiang D., Clifford D.B., Cordelli D.M., de Burca A., Demic N., Desguerre I., De Waele L., Di Fonzo A., Dunham S.R., Dyack S., Elmslie F., Ferrand M., Fisher G., Karimiani E.G., Ghoumid J., Gibbon F., Goel H., Hilmarsen H.T., Hughes I., Jacob A., Jones E.A., Kumar R., Leventer R.J., MacDonald S., Maroofian R., Mehta S.G., Metz I., Monfrini E., Neumann D., Noetzel M., O'Driscoll M., Ounap K., Panzer A., Parikh S., Prabhakar P., Ramond F., Sandford R., Saneto R., Soh C., Stutterd C.A., Subramanian G.M., Talbot K., Thomas R.H., Toro C., Touraine R., Wakeling E., Wassmer E., Whitney A., Livingston J.H., O'Keefe R.T., Badrock A.P. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Proband, 030105 genetics & heredity, Gene mutation, ribosomopathy, Compound heterozygosity, Genetic analysis, Loss of heterozygosity, Leukoencephalopathy, Consanguinity, Leukoencephalopathies, Pathology, Molecular, Child, Zebrafish, Genetics (clinical), Genetics, Molecular pathology, C/D box snoRNA U8, coats plus, Labrune syndrome, leukoencephalopathy with calcifications and cysts, SNORD118, Calcinosis, Middle Aged, 3. Good health, Child, Preschool, Female, Adult, Heterozygote, Adolescent, coats plu, Biology, Young Adult, 03 medical and health sciences, medicine, Animals, Humans, RNA, Small Nucleolar, Genetic Association Studies, Aged, leukoencephalopathy with calcifications and cyst, Infant, Newborn, Infant, medicine.disease, Disease Models, Animal, 030104 developmental biology |
| الوصف: | Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5' end and 3' extension of precursor-U8. There was no obvious genotype-phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3' end processing of precursor-U8. |
| وصف الملف: | STAMPA |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f2d9de564df3de6329454df9c446972Test http://hdl.handle.net/11585/786787Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1f2d9de564df3de6329454df9c446972 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |