Next Article in Journal
Chitosan or Cyclodextrin Grafted with Oleic Acid Self-Assemble into Stabilized Polymeric Micelles with Potential of Drug Carriers
Previous Article in Journal
Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Life
Volume 13
Issue 2
10.3390/life13020445
life-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

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

by
Cérane Cafournet
1,
Sofia Zanin
1,
Anne Guimier
2,3,
Marie Hully
4,
Zahra Assouline
5,
Giulia Barcia
5,
Pascale de Lonlay
6,
Julie Steffann
1,5,
Arnold Munnich
1,
Jean-Paul Bonnefont
1,5,
Agnès Rötig
1,
Benedetta Ruzzenente
1 and
Metodi D. Metodiev
1,*
1
Laboratory for Genetics of Mitochondrial Disorders, Imagine Institute, Université Paris Cité, INSERM U1163, 75015 Paris, France
2
Laboratory of Embryology and Genetics of Human Malformations, Imagine Institute, Université Paris Cité, INSERM U1163, 75015 Paris, France
3
Genomic Medicine Service for Rare Diseases, APHP.CUP, Necker Enfants Malades Hospital, 75015 Paris, France
4
Pediatric Neurology Department, Necker Enfants Malades Hospital, AP-HP, Institute Imagine, Université Paris Cité, INSERM U1163, 75015 Paris, France
5
Department of Genetics, Reference Center for Mitochondrial Diseases (CARAMMEL), Necker Enfants Malades Hospital, 75015 Paris, France
6
Reference Center for Inherited Metabolic Diseases, Necker Enfants Malades Hospital, Imagine Institute, Université Paris Cité, INEM-1151, G2M, MetabERN, 75015 Paris, France
*
Author to whom correspondence should be addressed.
Life 2023, 13(2), 445; https://doi.org/10.3390/life13020445
Submission received: 30 November 2022 / Revised: 30 January 2023 / Accepted: 1 February 2023 / Published: 4 February 2023
(This article belongs to the Section Physiology and Pathology)
Browse Figures
Versions Notes

Abstract

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.
Keywords: mitochondrial disease; ELAC2; RNA processing; cardiomyopathy; neurological disease mitochondrial disease; ELAC2; RNA processing; cardiomyopathy; neurological disease

Share and Cite

MDPI and ACS Style

Cafournet, C.; Zanin, S.; Guimier, A.; Hully, M.; Assouline, Z.; Barcia, G.; de Lonlay, P.; Steffann, J.; Munnich, A.; Bonnefont, J.-P.; et al. Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy. Life 2023, 13, 445. https://doi.org/10.3390/life13020445

AMA Style

Cafournet C, Zanin S, Guimier A, Hully M, Assouline Z, Barcia G, de Lonlay P, Steffann J, Munnich A, Bonnefont J-P, et al. Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy. Life. 2023; 13(2):445. https://doi.org/10.3390/life13020445

Chicago/Turabian Style

Cafournet, Cérane, Sofia Zanin, Anne Guimier, Marie Hully, Zahra Assouline, Giulia Barcia, Pascale de Lonlay, Julie Steffann, Arnold Munnich, Jean-Paul Bonnefont, and et al. 2023. "Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy" Life 13, no. 2: 445. https://doi.org/10.3390/life13020445

APA Style

Cafournet, C., Zanin, S., Guimier, A., Hully, M., Assouline, Z., Barcia, G., de Lonlay, P., Steffann, J., Munnich, A., Bonnefont, J.-P., Rötig, A., Ruzzenente, B., & Metodiev, M. D. (2023). Novel ELAC2 Mutations in Individuals Presenting with Variably Severe Neurological Disease in the Presence or Absence of Cardiomyopathy. Life, 13(2), 445. https://doi.org/10.3390/life13020445

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop