Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings

2020 ◽  
pp. jclinpath-2020-207026
Author(s):  
Surita Meldau ◽  
Elizabeth Patricia Owen ◽  
Kashief Khan ◽  
Gillian Tracy Riordan
Keyword(s):  
South Africa ◽  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Molecular Genetic ◽  
Mitochondrial Diseases ◽  
Pathogenic Variant ◽  
Sub Saharan Africa ◽  
Inborn Errors ◽  
Birth Prevalence ◽  
Positive Results

AimsMitochondrial diseases form one of the largest groups of inborn errors of metabolism. The birth prevalence is approximately 1/5000 in well-studied populations, but little has been reported from Sub-Saharan Africa. The aim of this study was to describe the genetics underlying mitochondrial disease in South Africa.MethodsAn audit was performed on all mitochondrial disease genetic testing performed in Cape Town, South Africa.ResultsOf 1614 samples tested for mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) variants in South Africa between 1994 and 2019, there were 155 (9.6 %) positive results. Pathogenic mtDNA variants accounted for 113 (73%)/155, from 96 families. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, 37 (33%)/113, Leber’s hereditary optic neuropathy, 26 (23%)/113, and single large mtDNA deletions, 22 (20%)/113, accounted for 76%. Thirty eight of 42 nDNA-positive results were homozygous for the MPV17 pathogenic variant c.106C>T (p.[Gln36Ter, Ser25Profs*49]) causing infantile neurohepatopathy, one of the largest homozygous groups reported in the literature. The other nDNA variants were in TAZ1, CPT2, BOLA3 and SERAC1. None were identified in SURF1, POLG or PDHA1.ConclusionsFinding a large group with a homozygous nuclear pathogenic variant emphasises the importance of looking for possible founder effects. The absence of other widely described pathogenic nDNA variants in this cohort may be due to reduced prevalence or insufficient testing. As advances in therapeutics develop, it is critical to develop diagnostic platforms on the African subcontinent so that population-specific genetic variations can be identified.

A review of mitochondrial disease in dogs

2021 ◽  
Vol 26 (10) ◽  
pp. 1-8
Author(s):  
Sergio A Gomes
Keyword(s):  
Mitochondrial Disease ◽  
Genetic Basis ◽  
Nuclear Dna ◽  
Mitochondrial Diseases ◽  
Unknown Origin ◽  
Eukaryotic Cells ◽  
Genetic Mutations ◽  
Ataxic Neuropathy ◽  
Clinical Syndromes ◽  
Cellular Organelles

Mitochondria are maternally inherited cellular organelles located in the cytoplasm of most eukaryotic cells. Mitochondrial diseases are a type of metabolic disorder, involving the respiratory chain under the control of both the mitochondrial DNA and nuclear DNA. In dogs, mitochondriopathies are considered rare, with few clinical syndromes having had their structural, biochemical and genetic basis identified. In this review, the basis for suspecting a mitochondrial disease clinically is summarised, with particular focus on mitochondrial encephalopathies, encephalomyelopathies and neuropathies. Recognisable confirmed mitochondriopathies including spongiform leukoencephalomyelopathy, Alaskan Husky encephalopathy, Leigh-like subacute necrotising encephalopathy and sensory ataxic neuropathy in the Golden Retriever are described in detail, alongside previously reported individual cases of presumptive mitochondriopathies of unknown origin. Genetic mutations reported in the literature are reviewed. A clear classification for mitochondrial diseases in veterinary medicine is lacking, and this review is the first to address this class of diseases specifically in dogs.

Le encefalomiopatie mitocondriali

1996 ◽  
Vol 9 (6) ◽  
pp. 775-780 ◽  
Author(s):  
E. Ciceri ◽  
I. Moroni ◽  
G. Uziel ◽  
M. Savoiardo
Keyword(s):  
Mitochondrial Dna ◽  
Respiratory Chain ◽  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Molecular Genetic ◽  
Neuromuscular Diseases ◽  
Disease Classification ◽  
Respiratory Chain Complexes ◽  
Enzyme Defect ◽  
Mitochondrial Encephalomyopathies

The mitochondrial encephalomyopathies are relatively rare neuromuscular diseases clinically characterised by myopathy and encephalopathy caused by structurally or functionally impaired mitochondria. The biochemical hallmark of this group of disorders is impaired mitochondrial energy production: Kreb's cycle, respiratory chain, oxidative phosphorylation and beta-oxidation of fatty acids. The presence of lactic acidosis and ragged red fibres, i.e. subsarcolemmal accumulations of abnormally sized mitochondria are highly indicative findings for mitochondrial disease. Classification and diagnostic criteria are based on biochemical findings with a search for specific enzyme deficit and molecular genetic information. Molecular genetic studies aim to identify the mitochondrial DNA changes responsible for the enzyme defect. Ragged red fibres are not essential for diagnosis as they are not present in some diseases. In rare cases, mitochondrial diseases are caused by nuclear DNA defects or, more commonly a mitochondrial DNA deficit. Diagnosis may prove difficult given the pathogenetic complexity and clinical and phenotypical variability of these conditions. Despite indirect symptoms of mitochondrial disease, the enzyme defect and genetic alteration cannot be identified in some cases. The mitochondrial encephalopathies can be classified according to the metabolic pathways involved into impaired transport ot uptake of energy, impaired Kreb's cycle or respiratory chain complexes or complex defects due to mitochondrial DNA changes.

scholarly journals Endocrine Disorders in Primary Mitochondrial Disease

2018 ◽  
Vol 2 (4) ◽  
pp. 361-373 ◽  
Author(s):  
Iman S Al-Gadi ◽  
Richard H Haas ◽  
Marni J Falk ◽  
Amy Goldstein ◽  
Shana E McCormack
Keyword(s):  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Molecular Genetic ◽  
Point Mutations ◽  
High Risk Population ◽  
Endocrine Disorders ◽  
Screening Practices ◽  
Abnormal Growth ◽  
The North ◽  
Adult Participants

Abstract Context Endocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated age-stratified estimates of the prevalence of endocrine conditions are needed. Objective To measure the point prevalence of selected endocrine disorders in individuals with mitochondrial disease. Design, Setting, and Patients The North American Mitochondrial Disease Consortium Patient Registry is a large, prospective, physician-curated cohort study of individuals with mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of primary mitochondrial disease confirmed by molecular genetic testing. Main Outcome Measures Age-specific prevalence of diabetes mellitus (DM), abnormal growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism. Results The majority of our sample was pediatric (<18 years; 60.1%), female (56.9%), and white (85.9%). DM affected 2% of participants aged <18 years [95% confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI: 18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS; 31.9%, of whom 86.2% had the m.3243A>G mutation). DM occurred more often with mitochondrial DNA defects (point mutations and/or deletions) than with nuclear DNA mutations (23.3% vs 3.7%, respectively; P < 0.001). Other prevalence estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%) for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism. Conclusion DM and AGSM are highly prevalent in primary mitochondrial disease. Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre/Pearson syndrome spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical screening practices should reflect the substantial prevalence of endocrine disorders in mitochondrial disease.

scholarly journals Pathology of Adult and Paediatric Mitochondrial Myopathies

2017 ◽  
Author(s):  
Rahul Phadke
Keyword(s):  
Nuclear Dna ◽  
Molecular Genetic ◽  
Mitochondrial Diseases ◽  
Molecular Genetic Analysis ◽  
Muscle Pathology ◽  
Respiratory Chain Enzyme ◽  
Metabolic Functions ◽  
Atp Generation ◽  
Next Generation Sequencing Ngs

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

African Islam and Islam in Africa

2009 ◽  
Vol 26 (3) ◽  
pp. i-xi
Author(s):  
Ali A. Mazrui
Keyword(s):  
South Africa ◽  
Muslim World ◽  
Sub Saharan Africa ◽  
Black Africa ◽  
Sub Saharan ◽  
Definition Of

Sub-Saharan Africa is often regarded as part of the periphery, rather thanpart of the center, of the Muslim world. In the Abrahamic world, Africa isoften marginalized. But is there anything special about Islam’s relationshipwith Africa? Are there unique aspects of African Islam? Islam has exerted anenormous influence upon Africa and its peoples; but has Africa had anyimpact upon Islam? While the impressive range of articles presented in thisspecial issue do not directly address such questions, my short editorialattempts to put those articles within the context of Africa’s uniqueness in theannals of Islam. One note: Although these articles concentrate on sub-Saharan Africa (“Black Africa”), our definition of Africa encompasses thecontinent as a whole – from South Africa to Egypt, Angola to Algeria, andMozambique to Mauritania ...

scholarly journals HIV and cardiovascular disease in sub-Saharan Africa: Demographic and Health Survey data for 4 countries

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Leonard E. Egede ◽  
Rebekah J. Walker ◽  
Patricia Monroe ◽  
Joni S. Williams ◽  
Jennifer A. Campbell ◽  
...  
Keyword(s):  
South Africa ◽  
Cardiovascular Disease ◽  
Health Survey ◽  
Survey Design ◽  
Logistic Models ◽  
Population Data ◽  
Demographic And Health Survey ◽  
Sub Saharan Africa ◽  
Sub Saharan ◽  
The Relationship

Abstract Background Investigate the relationship between two common cardiovascular diseases and HIV in adults living in sub-Saharan Africa using population data provided through the Demographic and Health Survey. Methods Data for four sub-Saharan countries were used. All adults asked questions regarding diagnosis of HIV, diabetes, and hypertension were included in the sample totaling 5356 in Lesotho, 3294 in Namibia, 9917 in Senegal, and 1051 in South Africa. Logistic models were run for each country separately, with self-reported diabetes as the first outcome and self-reported hypertension as the second outcome and HIV status as the primary independent variable. Models were adjusted for age, gender, rural/urban residence and BMI. Complex survey design allowed weighting to the population. Results Prevalence of self-reported diabetes ranged from 3.8% in Namibia to 0.5% in Senegal. Prevalence of self-reported hypertension ranged from 22.9% in Namibia to 0.6% in Senegal. In unadjusted models, individuals with HIV in Lesotho were 2 times more likely to have self-reported diabetes (OR = 2.01, 95% CI 1.08–3.73), however the relationship lost significance after adjustment. Individuals with HIV were less likely to have self-reported diabetes after adjustment in Namibia (OR = 0.29, 95% CI 0.12–0.72) and less likely to have self-reported hypertension after adjustment in Lesotho (OR = 0.63, 95% CI 0.47–0.83). Relationships were not significant for Senegal or South Africa. Discussion HIV did not serve as a risk factor for self-reported cardiovascular disease in sub-Saharan Africa during the years included in this study. However, given the growing prevalence of diabetes and hypertension in the region, and the high prevalence of undiagnosed cardiovascular disease, it will be important to continue to track and monitor cardiovascular disease at the population level and in individuals with and without HIV. Conclusions The odds of self-reported diabetes in individuals with HIV was high in Lesotho and low in Namibia, while the odds of self-reported hypertension in individuals with HIV was low across all 4 countries included in this study. Programs are needed to target individuals that need to manage multiple diseases at once and should consider increasing access to cardiovascular disease management programs for older adults, individuals with high BMI, women, and those living in urban settings.

scholarly journals Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001510
Author(s):  
Albert Zishen Lim ◽  
Daniel M Jones ◽  
Matthew G D Bates ◽  
Andrew M Schaefer ◽  
John O'Sullivan ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Laboratory Data ◽  
Nuclear Genome ◽  
Nuclear Gene ◽  
Left Ventricular ◽  
Adult Patients ◽  
Limited Information ◽  
Cardiac Abnormalities ◽  
Cardiac Manifestations

ObjectiveRegular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.MethodsAdult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.ResultsIn this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001).ConclusionsOur findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.

scholarly journals Relationships with caregivers and mental health outcomes among adolescents living with HIV: a prospective cohort study in South Africa

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yulia Shenderovich ◽  
Mark Boyes ◽  
Michelle Degli Esposti ◽  
Marisa Casale ◽  
Elona Toska ◽  
...  
Keyword(s):  
Mental Health ◽  
South Africa ◽  
Cohort Study ◽  
Mental Health Problems ◽  
Health Problems ◽  
Sub Saharan Africa ◽  
Depression Symptoms ◽  
Sub Saharan ◽  
Positive Caregiving ◽  
Living With Hiv

Abstract Background Mental health problems may impact adherence to anti-retroviral treatment, retention in care, and consequently the survival of adolescents living with HIV. The adolescent-caregiver relationship is an important potential source of resilience. However, there is a lack of longitudinal research in sub-Saharan Africa on which aspects of adolescent-caregiver relationships can promote mental health among adolescents living with HIV. We draw on a prospective longitudinal cohort study undertaken in South Africa to address this question. Methods The study traced adolescents aged 10–19 initiated on antiretroviral treatment in government health facilities (n = 53) within a health district of the Eastern Cape province. The adolescents completed standardised questionnaires during three data collection waves between 2014 and 2018. We used within-between multilevel regressions to examine the links between three aspects of adolescent-caregiver relationships (caregiver supervision, positive caregiving, and adolescent-caregiver communication) and adolescent mental health (depression symptoms and anxiety symptoms), controlling for potential confounders (age, sex, rural/urban residence, mode of infection, household resources), n=926 adolescents. Results Improvements in caregiver supervision were associated with reductions in anxiety (0.98, 95% CI 0.97–0.99, p=0.0002) but not depression symptoms (0.99, 95% CI 0.98–1.00, p=.151), while changes in positive caregiving were not associated with changes in mental health symptoms reported by adolescents. Improvements in adolescent-caregiver communication over time were associated with reductions in both depression (IRR=0.94, 95% CI 0.92–0.97, p<.0001) and anxiety (0.91, 95% CI 0.89–0.94, p<.0001) symptoms reported by adolescents. Conclusions Findings highlight open and supportive adolescent-caregiver communication and good caregiver supervision as potential factors for guarding against mental health problems among adolescents living with HIV in South Africa. Several evidence-informed parenting programmes aim to improve adolescent-caregiver communication and caregiver supervision, and their effect on depression and anxiety among adolescents living with HIV should be rigorously tested in sub-Saharan Africa. How to improve communication in other settings, such as schools and clinics, and provide communication support for caregivers, adolescents, and service providers through these existing services should also be considered.

scholarly journals Climate Change and Health Preparedness in Africa: Analysing Trends in Six African Countries

2021 ◽  
Vol 18 (9) ◽  
pp. 4672
Author(s):  
Samuel Kwasi Opoku ◽  
Walter Leal Filho ◽  
Fudjumdjum Hubert ◽  
Oluwabunmi Adejumo
Keyword(s):  
Public Health ◽  
Climate Change ◽  
South Africa ◽  
Human Health ◽  
Health Systems ◽  
Health Professionals ◽  
Health Problems ◽  
Sub Saharan Africa ◽  
Basic Knowledge ◽  
African Countries

Climate change is a global problem, which affects the various geographical regions at different levels. It is also associated with a wide range of human health problems, which pose a burden to health systems, especially in regions such as Africa. Indeed, across the African continent public health systems are under severe pressure, partly due to their fragile socioeconomic conditions. This paper reports on a cross-sectional study in six African countries (Ghana, Nigeria, South Africa, Namibia, Ethiopia, and Kenya) aimed at assessing their vulnerabilities to climate change, focusing on its impacts on human health. The study evaluated the levels of information, knowledge, and perceptions of public health professionals. It also examined the health systems’ preparedness to cope with these health hazards, the available resources, and those needed to build resilience to the country’s vulnerable population, as perceived by health professionals. The results revealed that 63.1% of the total respondents reported that climate change had been extensively experienced in the past years, while 32% claimed that the sampled countries had experienced them to some extent. Nigerian respondents recorded the highest levels (67.7%), followed by Kenya with 66.6%. South Africa had the lowest level of impact as perceived by the respondents (50.0%) when compared with the other sampled countries. All respondents from Ghana and Namibia reported that health problems caused by climate change are common in the two countries. As perceived by the health professionals, the inadequate resources reiterate the need for infrastructural resources, medical equipment, emergency response resources, and technical support. The study’s recommendations include the need to improve current policies at all levels (i.e., national, regional, and local) on climate change and public health and to strengthen health professionals’ skills. Improving the basic knowledge of health institutions to better respond to a changing climate is also recommended. The study provides valuable insights which may be helpful to other nations in Sub-Saharan Africa.

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