POLRMT mutations impair mitochondrial transcription causing neurological disease

On 18 February, 2021, professor Robert W.Taylor from Newcastle University and Claes M.Gustafsson from University of Gothenburg published a paper on Nature communications. The paper titled POLRMT mutations impair mitochondrial transcription causing neurological disease.

While >300 disease-causing variants have been identifified in the mitochondrial DNA (mtDNA) polymerase γ, 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 identififies recessive and dominant variants in the POLRMT gene. Patient fifibroblasts 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 effffects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism.

The nervous system is a system that plays a dominant role in the regulation of physiological functions in the body. It is mainly composed of nerve tissue and is divided into two parts: the central nervous system and the peripheral nervous system. The central nervous system in turn includes the brain and spinal cord, and the peripheral nervous system includes the cranial nerves and spinal nerves. In biological individuals, exercise the role of "command" and control the coordination of various tissues and organs of the body. Neurological diseases may be caused by external factors or personal genetic factors, including cerebrovascular diseases, periodic paralysis, progressive muscular dystrophy, myotonic dystrophy, and ataxia. Nervous system diseases are diffiffifficult to cure at the current medical level, mainly relying on early prevention and treatment. Therefore, early diagnosis and early intervention are of great significance for improving the long-term prognosis of neurological diseases.With the rapid development of genomics, proteomics and metabolomics, some indicators related to the occurrence or development of nervous system diseases, such as BDNF, GFAP, SAA, etc., have been found to be early diagnosis of some neurological diseases. An indicator of prognostic diagnosis.