Dafsari, Hormos Salimi, Kocaturk, Nur Mehpare, Daimagueler, Huelya-Sevcan, Brunn, Anna, Doetsch, Joerg, Weis, Joachim, Deckert, Martina and Cirak, Sebahattin (2019). Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B are a cause for congenital myopathy. Acta Neuropathol. Commun., 7 (1). LONDON: BMC. ISSN 2051-5960
Full text not available from this repository.Abstract
Congenital myopathies (CM) form a genetically heterogeneous group of disorders characterized by perinatal muscle weakness. Here, we report an 11-year old male offspring of consanguineous parents of Lebanese origin. He presented with proximal weakness including Gower's sign, and skeletal muscle biopsy revealed myopathic changes with core-like structures. Whole exome sequencing of this index patient lead to the discovery of a novel genetically defined CM subtype based on bi-allelic mutations in the uncoordinated mutant number-45 myosin chaperone B (UNC45B) NM_173167:c.2261G > A, p.Arg754Gln. The mutation is conserved in evolution and co-segregates within the pedigree with the phenotype, and located in the myosin binding armadillo repeat domain 3 (ARM3), and has a CADD Score of 35. On a multimeric level, UNC45B aggregates to a chain which serves as an assembly line and functions as a template defining the geometry, regularity, and periodicity of myosin arranged into muscle thick filaments. Our discovery is in line with the previously described myopathological phenotypes in C. elegans and in vertebrate mutants and knockdown-models. In conclusion, we here report for the first time a patient with an UNC45B mutation causing a novel genetically defined congenital myopathy disease entity.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
| Creators: |
|
||||||||||||||||||||||||||||||||||||
| URN: | urn:nbn:de:hbz:38-124205 | ||||||||||||||||||||||||||||||||||||
| DOI: | 10.1186/s40478-019-0869-1 | ||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Acta Neuropathol. Commun. | ||||||||||||||||||||||||||||||||||||
| Volume: | 7 | ||||||||||||||||||||||||||||||||||||
| Number: | 1 | ||||||||||||||||||||||||||||||||||||
| Date: | 2019 | ||||||||||||||||||||||||||||||||||||
| Publisher: | BMC | ||||||||||||||||||||||||||||||||||||
| Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||
| ISSN: | 2051-5960 | ||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||
| Uncontrolled Keywords: |
|
||||||||||||||||||||||||||||||||||||
| Refereed: | Yes | ||||||||||||||||||||||||||||||||||||
| URI: | http://kups.ub.uni-koeln.de/id/eprint/12420 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
 |
View Item |