-
Chinese Medical Journal Apr 2019
Topics: Adult; DNA, Mitochondrial; Electroencephalography; Humans; MERRF Syndrome; Male; Mitochondrial Myopathies; Mutation; RNA, Transfer, Asn
PubMed: 30897601
DOI: 10.1097/CM9.0000000000000151 -
Frontiers in Neurology 2019Lipomas have often been associated with mtDNA mutations and were mainly observed in patients with mutation in mitochondrial tRNAlysine which is also the most frequent...
Lipomas have often been associated with mtDNA mutations and were mainly observed in patients with mutation in mitochondrial tRNAlysine which is also the most frequent mutation associated with MERRF. Up to date, no systematic studies have been developed in order to assess the incidence of lipomas in large cohorts of mitochondrial patients.The aim of this study is to analyze the incidence and characteristics of lipomas among an Italian cohort of patients with mitochondrial diseases. A retrospective, database-based study (Nation-wide Italian Collaborative Network of Mitochondrial Diseases) of patients with lipomas was performed. A total of 22 (1.7%) patients with lipomas have been identified among the 1,300 mitochondrial patients, enrolled in the Italian database. In about 18% multiple systemic lipomatosis (MSL) was the only clinical manifestation; 54% of patients showed a classical MERRF syndrome. Myopathy, alone or in association with other symptoms, was found in 27% of patients. Lactate was elevated in all the 12 patients in which was measured. Muscle biopsy was available in 18/22 patients: in all of them mitochondrial abnormalities were present. Eighty six percent had mutations in mtDNA coding for tRNA lysine. In most of patients, lipomas were localized along the cervical-cranial-thoracic region. In 68% of the patients were distributed symmetrically. Only two patients had lipomas in a single anatomical site (1 in right arm and 1 in gluteus maximum). MSL is often overlooked by clinicians in patients with mitochondrial diseases where the clinical picture could be dominated by a severe multi-systemic involvement. Our data confirmed that MSL is a rare sign of mitochondrial disease with a strong association between multiple lipomas and lysine tRNA mutations. MSL could be considered, even if rare, a red flag for mitochondrial disorders, even in patients with an apparently isolated MSL.
PubMed: 30873109
DOI: 10.3389/fneur.2019.00160 -
Chinese Medical Journal Mar 2019
Topics: Anticonvulsants; Clonazepam; Female; Humans; Levetiracetam; MERRF Syndrome; Male; Myoclonus
PubMed: 30807362
DOI: 10.1097/CM9.0000000000000042 -
Biochimica Et Biophysica Acta.... May 2019Mitochondrial diseases are a group of rare heterogeneous genetic disorders caused by total or partial mitochondrial dysfunction. They can be caused by mutations in...
Mitochondrial diseases are a group of rare heterogeneous genetic disorders caused by total or partial mitochondrial dysfunction. They can be caused by mutations in nuclear or mitochondrial DNA (mtDNA). MERRF (Myoclonic Epilepsy with Ragged-Red Fibers) syndrome is one of the most common mitochondrial disorders caused by point mutations in mtDNA. It is mainly caused by the m.8344A > G mutation in the tRNA (UUR) gene of mtDNA (MT-TK gene). This mutation affects the translation of mtDNA encoded proteins; therefore, the assembly of the electron transport chain (ETC) complexes is disrupted, leading to a reduced mitochondrial respiratory function. However, the molecular pathogenesis of MERRF syndrome remains poorly understood due to the lack of appropriate cell models, particularly in those cell types most affected in the disease such as neurons. Patient-specific induced neurons (iNs) are originated from dermal fibroblasts derived from different individuals carrying the particular mutation causing the disease. Therefore, patient-specific iNs can be used as an excellent cell model to elucidate the mechanisms underlying MERRF syndrome. Here we present for the first time the generation of iNs from MERRF dermal fibroblasts by direct reprograming, as well as a series of pathophysiological characterizations which can be used for testing the impact of a specific mtDNA mutation on neurons and screening for drugs that can correct the phenotype.
Topics: Adult; Cellular Reprogramming; Cellular Reprogramming Techniques; DNA, Mitochondrial; Dermis; Fibroblasts; Humans; MERRF Syndrome; Male; Middle Aged; Neurons; Point Mutation
PubMed: 30797798
DOI: 10.1016/j.bbamcr.2019.02.010 -
Polish Journal of Pathology : Official... 2018Our studies concerned skeletal muscle biopsy specimens from a patient with clinically suspected MERRF syndrome, confirmed by genetic tests showing the presence of point...
Our studies concerned skeletal muscle biopsy specimens from a patient with clinically suspected MERRF syndrome, confirmed by genetic tests showing the presence of point mutation in the m.8344A> G in the tRNALys gene. Ultrastructurally, extensive damage of mitochondria in skeletal muscle fibres was observed, including the presence of two types of mitochondrial inclusions. Mild damage of mitochondria was revealed in small blood vessels and the presence of calcium deposits in the vascular walls were observed. The differences in mitochondrial damage may be related to different origin and expenditure of biologically useful energy in these cells.
Topics: Humans; MERRF Syndrome; Microvessels; Mitochondria; Muscle Fibers, Skeletal; Mutation
PubMed: 30786693
DOI: 10.5114/pjp.2018.80904 -
Case Reports in Neurological Medicine 2018Mitochondrial (mt) tRNA (MTT) gene mutations are an important cause of mitochondrial diseases and are associated with a wide range of clinical presentations. Most...
Mitochondrial (mt) tRNA (MTT) gene mutations are an important cause of mitochondrial diseases and are associated with a wide range of clinical presentations. Most mutations fall into three mitochondrial tRNAs (tRNAIle, tRNALeu (UUR), and tRNALys) and are responsible for half of the mitochondrial diseasees associated with tRNA mutation, with MERRF, MELAS, mitochondrial myopathy, and Leigh syndrome being the most frequent phenotypes. More than 100 tRNA pathogenetic mutations are described, showing little correlation between the observed clinical phenotype and a specific mitochondrial tRNA mutation. Furthermore different mutation can manifest with similar clinical phenotypes, making the genotype-phenotype correlation difficult. Here we report the case of an Italian 53-year-old woman presenting with a proximal myopathy and the m.5835G>A mutation in MT-TY gene coding for the mitochondrial tRNA Tyrosine gene.
PubMed: 30643656
DOI: 10.1155/2018/8406712 -
European Annals of Otorhinolaryngology,... Apr 2019Patients with MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibres) usually present with encephalomyopathy. However, progressive, recurrent cervicothoracic...
INTRODUCTION
Patients with MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibres) usually present with encephalomyopathy. However, progressive, recurrent cervicothoracic lipomatosis may be rarely observed.
CASE REPORT
The authors report 4 cases of MERRF syndrome associated with lipomatosis. In 3 patients, the diagnosis of MERRF syndrome was established on the basis of the clinical features of the lipomas and clinical interview revealing a personal or family history of lipomas and myopathy.
DISCUSSION
In the presence of extensive spinal lipomatosis, the presence of other clinical signs of MERRF syndrome in the patient or the patient's family must be investigated. A diagnosis of MERRF syndrome can guide appropriate genetic counselling.
Topics: Adult; Female; Humans; Lipomatosis; MERRF Syndrome; Male; Middle Aged; Neck; Siblings; Spinal Neoplasms; Thorax
PubMed: 30409749
DOI: 10.1016/j.anorl.2018.10.015 -
Urology Case Reports Jan 2019
PubMed: 30364532
DOI: 10.1016/j.eucr.2018.10.006 -
Chinese Medical Journal Oct 2018
Topics: DNA, Mitochondrial; Epilepsies, Myoclonic; Glutamic Acid; Humans; MERRF Syndrome; RNA, Transfer
PubMed: 30334547
DOI: 10.4103/0366-6999.243575 -
Chinese Medical Journal Oct 2018
Topics: DNA, Mitochondrial; Epilepsies, Myoclonic; Humans; MERRF Syndrome; RNA, Transfer
PubMed: 30334546
DOI: 10.4103/0366-6999.243557