Chorea, psychosis, acanthocytosis, and prolonged survival associated with
            <i>ELAC2</i>
            mutations

Paucar, Martin; Pajak, Aleksandra; Freyer, Christoph; Bergendal, Åsa; Döry, Margit; Laffita-Mesa, José Miguel; Stranneheim, Henrik; Lagerstedt‐Robinson, Kristina; Savitcheva, Irina; Walker, Ruth H.; Wedell, Anna; Wredenberg, Anna; Svenningsson, Per

doi:10.1212/wnl.0000000000006320

Cited by 10 publications

(8 citation statements)

References 6 publications

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“…“Familial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy” [ 31 ] was later found to be caused by a GLUT1 mutation [ 32 ]; acanthocytes have additionally been reported in a variety of neurogenetic disorders, e.g. with mutations of ELAC2 [ 33 ] or in aceruloplasminemia [ 34 ]. Such findings are intriguing, but terming these disorders “neuroacanthocytosis” only serves to perpetuate and increase the taxonomic confusion.…”

Section: Discussionmentioning

confidence: 99%

“Neuroacanthocytosis” – Overdue for a Taxonomic Update

Walker

Danek

2021

Tremor and Other Hyperkinetic Movements

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Section: Discussionmentioning

confidence: 99%

“Neuroacanthocytosis” – Overdue for a Taxonomic Update

Walker

Danek

2021

Tremor and Other Hyperkinetic Movements

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“…Pathological variants in ELAC2 have been shown to give rise to infantile hypertrophic cardiomyopathy, global developmental delay, and early death [170] . Rare patients have expressed abnormal involuntary movements, acanthocytosis, and psychosis and live into adulthood [171] . PNPase, encoded by PNPT1, is a critical enzyme in polycistronic mtRNA transcript metabolism and likely import [172] .…”

Section: Mitochondrial Mt-trna and Mt-mrna Processing And Stabilizationmentioning

confidence: 99%

Mitochondrial diseases: expanding the diagnosis in the era of genetic testing

Saneto¹

2020

jtgg

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Mitochondrial diseases are clinically and genetically heterogeneous. These diseases were initially described a little over three decades ago. Limited diagnostic tools created disease descriptions based on clinical, biochemical analytes, neuroimaging, and muscle biopsy findings. This diagnostic mechanism continued to evolve detection of inherited oxidative phosphorylation disorders and expanded discovery of mitochondrial physiology over the next two decades. Limited genetic testing hampered the definitive diagnostic identification and breadth of diseases. Over the last decade, the development and incorporation of massive parallel sequencing has identified approximately 300 genes involved in mitochondrial disease. Gene testing has enlarged our understanding of how genetic defects lead to cellular dysfunction and disease. These findings have expanded the understanding of how mechanisms of mitochondrial physiology can induce dysfunction and disease, but the complete collection of disease-causing gene variants remains incomplete. This article reviews the developments in disease gene discovery and the incorporation of gene findings with mitochondrial physiology. This understanding is critical to the development of targeted therapies.

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“…In mitochondria, both RNAseP and RNAseZ have been localized within the so-called RNA granules, which are sites of active RNA maturation [ 12 ]. Mutations in the genes encoding RNAseP and RNAseZ subunits have been linked to impaired precursor processing and tRNA maturation, OXPHOS deficiency and mitochondrial disease (MD) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…To date, twenty autosomal recessive variants in the ELAC2 gene have been linked to MD, most commonly presenting with cardiomyopathy, developmental delay and lactic acidosis. Severe cardiomyopathy was usually associated with a poor prognosis in pediatric patients, while cases with milder forms had a prolonged survival, but variably severe neurological presentation [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Isolated complex I or combined complex I and IV deficiency were observed in patient biopsies and, sometimes, in fibroblast cultures consistent with the important role of ELAC2 in mtDNA expression.…”

Section: Introductionmentioning

confidence: 99%

Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy

Cafournet

Zanin

Guimier

et al. 2023

Life

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Transcription of mitochondrial DNA generates long polycistronic precursors whose nucleolytic cleavage yields the individual mtDNA-encoded transcripts. In most cases, this cleavage occurs at the 5′- and 3′-ends of tRNA sequences by the concerted action of RNAseP and RNaseZ/ELAC2 endonucleases, respectively. Variants in the ELAC2 gene have been predominantly linked to severe to mild cardiomyopathy that, in its milder forms, is accompanied by variably severe neurological presentations. Here, we report five patients from three unrelated families. Four of the patients presented mild to moderate cardiomyopathy and one died at 1 year of age, one patient had no evidence of cardiomyopathy. The patients had variable neurological presentations that included intellectual disability, ataxia, refractory epilepsy, neuropathy and deafness. All patients carried previously unreported missense and nonsense variants. Enzymatic analyses showed multiple OXPHOS deficiencies in biopsies from two patients, whereas immunoblot analyses revealed a decreased abundance of ELAC2 in fibroblasts from three patients. Northern blot analysis revealed an accumulation of unprocessed mt-tRNAVal-precursor consistent with the role of ELAC2 in transcript processing. Our study expands the genetic spectrum of ELAC2-linked disease and suggests that cardiomyopathy is not an invariably present clinical hallmark of this pathology.

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Chorea, psychosis, acanthocytosis, and prolonged survival associated with ELAC2 mutations

Cited by 10 publications

References 6 publications

“Neuroacanthocytosis” – Overdue for a Taxonomic Update

“Neuroacanthocytosis” – Overdue for a Taxonomic Update

Mitochondrial diseases: expanding the diagnosis in the era of genetic testing

Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy

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