POLRMT mutations impair mitochondrial transcription causing neurological disease
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00541626" target="_blank" >RIV/67985823:_____/21:00541626 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/21:10427555
Result on the web
<a href="https://www.nature.com/articles/s41467-021-21279-0" target="_blank" >https://www.nature.com/articles/s41467-021-21279-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-021-21279-0" target="_blank" >10.1038/s41467-021-21279-0</a>
Alternative languages
Result language
angličtina
Original language name
POLRMT mutations impair mitochondrial transcription causing neurological disease
Original language description
While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase gamma, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood, one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism. POLRMT is key for transcription of the mitochondrial genome, yet has not been implicated in mitochondrial disease to date. Here, the authors identify mutations in POLRMT in individuals with mitochondrial disease-related phenotypes and characterise underlying defects in mitochondrial transcription.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
12
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
13
Pages from-to
1135
UT code for WoS article
000621426600002
EID of the result in the Scopus database
2-s2.0-85100963543