Leigh syndrome caused by mitochondrial DNA-maintenance defects revealed by whole exome sequencing

Souza, Paulo Victor Sgobbi de; Bortholin, Thiago; Teixeira, Carlos Alberto Castro; Seneor, Daniel Delgado; Marin, Vitor Dias Gomes Barrios; Dias, Renan Braido; Farias, Igor Braga; Badia, Bruno de Mattos Lombardi; Silva, Luiz Henrique Libardi; Pinto, Wladimir Bocca Vieira de Rezende; Oliveira, Acary Souza Bullé; DiMauro, Salvatore

doi:10.1016/j.mito.2019.06.008

Cited by 6 publications

(2 citation statements)

References 38 publications

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“…SLC25A4, an inner transmembrane mitochondrial channel to ADP-ATP, displayed unusual central nervous system abnormalities consistent with LS. RNASEH1, an endonuclease to degrade RNA, manifested late-onset LS with progressive parkinsonism, pes cavus and cerebellar ataxia [56]. Even though the most common causes in mtDNA LS/LLS are point mutations or small deletions [7], DNA rearrangements (deletion) and depletion syndromes are rising in number accounts to mitochondrial disorders due to new genetic tools.…”

Section: Manganese Transportation Slc39a8mentioning

confidence: 99%

Molecular basis of Leigh syndrome: a current look

Baldo

Vilarinho

2020

Orphanet J Rare Dis

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Leigh Syndrome (OMIM 256000) is a heterogeneous neurologic disorder due to damage in mitochondrial energy production that usually starts in early childhood. The first description given by Leigh pointed out neurological symptoms in children under 2 years and premature death. Following cases brought some hypothesis to explain the cause due to similarity to other neurological diseases and led to further investigation for metabolic diseases. Biochemical evaluation and specific metabolic profile suggested impairment in energy production (OXPHOS) in mitochondria. As direct approach to involved tissues is not always possible or safe, molecular analysis is a great cost-effective option and, besides biochemical results, is required to confirm the underlying cause of this syndrome face to clinical suspicion. The Next Generation Sequencing (NGS) advance represented a breakthrough in molecular biology allowing simultaneous gene analysis giving short-time results and increasing the variants underlying this syndrome, counting over 75 monogenic causes related so far. NGS provided confirmation of emerging cases and brought up diagnosis in atypical presentations as late-onset cases, which turned Leigh into a heterogeneous syndrome with variable outcomes. This review highlights clinical presentation in both classic and atypical phenotypes, the investigation pathway throughout confirmation emphasizing the underlying genetic heterogeneity and increasing number of genes assigned to this syndrome as well as available treatment.

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Section: Manganese Transportation Slc39a8mentioning

confidence: 99%

Molecular basis of Leigh syndrome: a current look

Baldo

Vilarinho

2020

Orphanet J Rare Dis

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“…This association is defined as "LHON-MS", which is a distinct clinical phenotype with specific differences from LHON and MS, but also in this case the spinal cord abnormalities are rarely reported [5,11]. Similarly, spinal cord involvement rarely characterizes subjects with MELAS or Leigh syndrome [12][13][14]. The few publications in which this clinical aspect has been examined in detail were small case studies or retrospective studies of pediatric or juvenile patients.…”

Section: Discussionmentioning

confidence: 99%

Spinal Cord Involvement in Adult Mitochondrial Diseases: A Cohort Study

Primiano

Mariotti

Turrini

et al. 2021

Life

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The central nervous system is metabolically very demanding and consequently vulnerable to defects of the mitochondrial respiratory chain. While the clinical manifestations and the corresponding radiological findings of the brain involvement in mitochondrial diseases (e.g., stroke-like episodes, signal changes of the basal ganglia, cerebral and cerebellar atrophy) are well known, at present there are few data on the spinal-cord abnormalities in these pathologies, in particular in adult subjects. In this study, we present a cross-sectional cohort study on the prevalence and characterization of spinal-cord involvement in adult patients with genetically defined mitochondrial diseases.

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