scholarly journals Proximal Myopathy due to m.5835G>A Mutation in Mitochondrial MT-TY Gene

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
C. Simoncini ◽  
V. Montano ◽  
G. Alì ◽  
R. Costa ◽  
G. Siciliano ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Gene Mutations ◽  
Mitochondrial Diseases ◽  
Leigh Syndrome ◽  
Phenotype Correlation ◽  
Mitochondrial Trna ◽  
Gene Coding ◽  
Clinical Presentations ◽  
Wide Range ◽  
Proximal Myopathy

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.

scholarly journals Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

scholarly journals Hot topics in Fabry disease

2018 ◽  
Vol 94 (1118) ◽  
pp. 709-713 ◽  
Author(s):  
Tereza Cairns ◽  
Jonas Müntze ◽  
Judith Gernert ◽  
Lisa Spingler ◽  
Peter Nordbeck ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Gene Mutations ◽  
Lysosomal Storage ◽  
Neutralising Antibodies ◽  
Enzyme Replacement ◽  
Clinical Presentations ◽  
Wide Range ◽  
Therapy Effectiveness ◽  
Science Community ◽  
Rare Inborn Error

Fabry disease is a rare inborn error of the enzyme α-galactosidase (α-Gal) and results in lysosomal substrate accumulation in tissues with a wide range of clinical presentations. The disease has attracted a lot of interest over the last years, in particular since enzyme replacement therapy (ERT) has become widely available in 2001. With rising awareness and rising numbers of (diagnosed) patients, physicians encounter new challenges. Over 900 α-Gal gene mutations are currently known, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician and a lot of uncertainty for patients. Another challenge are patients who develop neutralising antibodies to ERT, which possibly leads to reduced therapy effectiveness. In this article, we summarise the latest developments in the science community regarding diagnostics and management of this rare lysosomal storage disorder and offer an outlook to future treatments.

scholarly journals Prevalence and Clinical Phenotype of the Triplicated α-Globin Genes and its Ethnic and Geographical Distribution in Guizhou of China

2020 ◽  
Author(s):  
Xi Luo ◽  
Shi-ping Chen ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Zhi-yu Peng ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background: Thalassemia is relatively epidemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype-phenotype correlation in this subpopulationMethods: A cohort of 7644 subjects was collected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results: We found that the frequency of α-globin triplication in Guizhou province was 0.759% (58/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the αααanti4.2/-α3.7 (HK αα) was 0.235% (18/7644), and the αααanti3.7/--SEA was 0.013% (1/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions: These data will be used to update the triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

scholarly journals Familial cases of subacute necrotizing encephalomyelopathy (Leigh syndrome)

2021 ◽  
Vol 4 (4) ◽  
pp. 370-374
Author(s):  
E.V. Shishkina ◽  
◽  
T.N. Bazilevskaya ◽  
I.V. Novikova ◽  
I.V. Leonova ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Genetic Diagnosis ◽  
Mitochondrial Diseases ◽  
Prenatal Testing ◽  
Leigh Syndrome ◽  
Diagnostic Techniques ◽  
Familial Cases ◽  
Gradual Loss ◽  
Clinical Presentations ◽  
System Disorder

Mitochondrial diseases are not uncommon. However, their genetic diagnosis is challenging for practitioners and requires up-to-date hightech methods. Early accurate diagnosis in first probands provides early preclinical genetic testing in all born children in compromised families and prenatal testing in future pregnancies, thereby allowing a differential planning of future pregnancies. This paper discusses a progressive central nervous system disorder, a congenital mitochondrial disease, subacute necrotizing encephalomyelopathy (Leigh syndrome). First, the authors briefly review etiology, prevalence, clinical presentations, diagnostic techniques, and treatment for this disease in children. Then, unique familial cases describing the diversity of clinical presentations are described. The diagnosis was genetically verified in all patients. MR signs always accompany the gradual loss of motor skills at early stages. Blood biochemistry identifies lactic acidosis. KEYWORDS: children, mitochondrial diseases, subacute necrotizing encephalomyelopathy, lactic acidosis, Leigh syndrome, diagnosis, mutations in the SURF1 gene. FOR CITATION: Shishkina E.V., Bazilevskaya T.N., Novikova I.V. et al. Familial cases of subacute necrotizing encephalomyelopathy (Leigh syndrome). Russian Journal of Woman and Child Health. 2021;4(4):370–374 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-370-374.

scholarly journals Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xin Wang ◽  
Yanyun Wang ◽  
Dingyuan Ma ◽  
Zhilei Zhang ◽  
Yahong Li ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Phenylalanine Hydroxylase ◽  
Laboratory Data ◽  
Molecular Characteristics ◽  
Phenotype Correlation ◽  
Common Amino Acid ◽  
Appropriate Treatment ◽  
Clinical Presentations ◽  
Average Current

Abstract Background Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China. Methods Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated. Results We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %). Conclusions This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.

A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome

2020 ◽  
Vol 58 (11) ◽  
pp. 1809-1817
Author(s):  
Miaomiao Du ◽  
Xiujuan Wei ◽  
Pu Xu ◽  
Anran Xie ◽  
Xiyue Zhou ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Complex I ◽  
Clinical Symptoms ◽  
Lactate Production ◽  
Mitochondrial Diseases ◽  
Leigh Syndrome ◽  
Extracellular Lactate ◽  
Next Generation Sequencing Ngs ◽  
Mutant Cells ◽  
Generation Sequencing

AbstractObjectivesLeigh syndrome (LS) is one of the most common mitochondrial diseases and has variable clinical symptoms. However, the genetic variant spectrum of this disease is incomplete.MethodsNext-generation sequencing (NGS) was used to identify the m.14430A > G (p.W82R) variant in a patient with LS. The pathogenesis of this novel complex I (CI) variant was verified by determining the mitochondrial respiration, assembly of CI, ATP, MMP and lactate production, and cell growth rate in cybrids with and without this variant.ResultsA novel m.14430A > G (p.W82R) variant in the NADH dehydrogenase 6 (ND6) gene was identified in the patient; the mutant loads of m.14430A > G (p.W82R) in the patient were much higher than those in his mother. Although the transmitochondrial cybrid-based study showed that mitochondrial CI assembly remains unaffected in cells with the m.14430G variant, control cells had significantly higher endogenous and CI-dependent mitochondrial respiration than mutant cells. Accordingly, mutant cells had a lower ATP, MMP and higher extracellular lactate production than control cells. Notably, mutant cells had impaired growth in a galactose-containing medium when compared to wild-type cells.ConclusionsA novel m.14430A > G (p.W82R) variant in the ND6 gene was identified from a patient suspected to have LS, and this variant impaired mitochondrial respiration by decreasing the activity of mitochondrial CI.

Compression neuropathies of the forearm: anatomy, clinical features and management

2021 ◽  
pp. 1-10
Author(s):  
Alexander Scarborough ◽  
Robert J MacFarlane ◽  
Michail Klontzas ◽  
Rui Zhou ◽  
Mohammad Waseem
Keyword(s):  
Peripheral Nerve ◽  
Brachial Plexus ◽  
Upper Limb ◽  
Peripheral Nerves ◽  
Clinical Presentation ◽  
Permanent Damage ◽  
Peripheral Nerve Lesions ◽  
Clinical Presentations ◽  
Wide Range ◽  
Prompt Diagnosis

The upper limb consists of four major parts: a girdle formed by the clavicle and scapula, the arm, the forearm and the hand. Peripheral nerve lesions of the upper limb are divided into lesions of the brachial plexus or the nerves arising from it. Lesions of the nerves arising from the brachial plexus are further divided into upper (proximal) or lower (distal) lesions based on their location. Peripheral nerves in the forearm can be compressed in various locations and by a wide range of pathologies. A thorough understanding of the anatomy and clinical presentations of these compression neuropathies can lead to prompt diagnosis and management, preventing possible permanent damage. This article discusses the aetiology, anatomy, clinical presentation and surgical management of compressive neuropathies of the upper limb.

scholarly journals Anti-MDA5 Antibody Dermatomyositis Overlap with Systemic Lupus Erythematosus: A Case Report and Review of the Literature

2016 ◽  
Vol 10 (1) ◽  
pp. 122-128 ◽  
Author(s):  
Emily C. Milam ◽  
Jacobo Futran ◽  
Andrew G. Franks Jr.
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Case Report ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Clinical Phenotype ◽  
Review Of The Literature ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Clinical Presentations

Background: Dermatomyositis (DM) is an autoimmune connective tissue disease that primarily targets the muscle, skin, and lungs. Many patients have autoantibodies that correspond to distinct clinical phenotypes. Melanoma differentiation-associated gene 5 (anti-MDA5) antibody, a specific antibody that targets the melanoma differentiation-associated gene 5 (MDA5), has been reported in DM cases and is significant for a distinct cutaneous presentation and rapidly progressive interstitial lung disease. Objective: Herein, we describe a patient with DM with a positive anti-MDA5 antibody and characteristic clinical phenotype, who subsequently developed coexisting systemic lupus erythematosus (SLE). A diagnosis of SLE was supported by his clinical phenotype, positive serologies, hypocomplementemia, and progression to glomerulonephritis and lupus cerebritis, features of which fulfilled the American College of Rheumatology criteria for SLE. Conclusion: DM is known to overlap with other autoimmune diseases, including SLE, and coexistence can lead to a wide variety of clinical presentations. SLE overlapping with anti-MDA5 positive DM may present with distinct clinical features.

scholarly journals AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome

Gene Therapy ◽  
2017 ◽  
Vol 24 (10) ◽  
pp. 661-667 ◽  
Author(s):  
I Di Meo ◽  
S Marchet ◽  
C Lamperti ◽  
M Zeviani ◽  
C Viscomi
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Clinical Phenotype ◽  
Leigh Syndrome

scholarly journals The Clinical Spectrum of Young Onset Dementia Points to Its Stochastic Origins

2021 ◽  
pp. 1-17
Author(s):  
Peter K. Panegyres
Keyword(s):  
Small Vessel Disease ◽  
Age Of Onset ◽  
Gene Mutations ◽  
Lewy Body Disease ◽  
Corticobasal Degeneration ◽  
Young Onset ◽  
Clinical Presentations ◽  
Eeg Data ◽  
Common Causes ◽  
Young Onset Dementia

Background: Dementia is a major global health problem and the search for improved therapies is ongoing. The study of young onset dementia (YOD)—with onset prior to 65 years—represents a challenge owing to the variety of clinical presentations, pathology, and gene mutations. The advantage of the investigation of YOD is the lack of comorbidities that complicate the clinical picture in older adults. Here we explore the origins of YOD. Objective: To define the clinical diversity of YOD in terms of its demography, range of presentations, neurological examination findings, comorbidities, medical history, cognitive findings, imaging abnormalities both structural and functional, electroencephagraphic (EEG) data, neuropathology, and genetics. Methods: A prospective 20-year study of 240 community-based patients referred to specialty neurology clinics established to elucidate the nature of YOD. Results: Alzheimer’s disease (AD; n = 139) and behavioral variant frontotemporal (bvFTD; n = 58) were the most common causes with a mean age of onset of 56.5 years for AD (±1 SD 5.45) and 57.1 years for bvFTD (±1 SD 5.66). Neuropathology showed a variety of diagnoses from multiple sclerosis, Lewy body disease, FTD-MND, TDP-43 proteinopathy, adult-onset leukoencephalopathy with axonal steroids and pigmented glia, corticobasal degeneration, unexplained small vessel disease, and autoimmune T-cell encephalitis. Non-amnestic forms of AD and alternative forms of FTD were discovered. Mutations were only found in 11 subjects (11/240 = 4.6%). APOE genotyping was not divergent between the two populations. Conclusion: There are multiple kinds of YOD, and most are sporadic. These observations point to their stochastic origins.

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