دورية أكاديمية
أعرض في EDS

Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.

التفاصيل البيبلوغرافية
العنوان: Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.
المؤلفون: Balicza P; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.; Eotvos Lorand Research Network, Multiomic Neurodegeneration Research Group, Budapest, Hungary., Gezsi A; Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary., Fedor M; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary., Sagi JC; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary., Gal A; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary., Varga NA; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary., Molnar MJ; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.; Eotvos Lorand Research Network, Multiomic Neurodegeneration Research Group, Budapest, Hungary.
المصدر: Frontiers in psychiatry [Front Psychiatry] 2024 Jan 05; Vol. 14, pp. 1301272. Date of Electronic Publication: 2024 Jan 05 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101545006 Publication Model: eCollection Cited Medium: Print ISSN: 1664-0640 (Print) Linking ISSN: 16640640 NLM ISO Abbreviation: Front Psychiatry Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Switzerland : Frontiers Research Foundation, 2010-
مستخلص: We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predominant negative psychiatric symptoms associated with rigidity. Clinical examinations showed multisystemic involvement. Together with elevated ergometric lactate levels, the clinical picture suggested mitochondrial disease, which was also supported by muscle histopathology. Exploratory transcriptome analysis also revealed the involvement of metabolic and oxidative phosphorylation pathways. Whole-exome sequencing identified a pathogenic MECP2 variant, which can explain both the dopamine imbalance and mitochondrial dysfunction in this patient. Mitochondrial dysfunction was previously suggested in classical Rett syndrome, and we detected related phenotype evidence on multiple consistent levels for the first time in a MECP2 variant carrier male. This study further supports the importance of the MECP2 gene in the mitochondrial pathways, which can open the gate for more personalized therapeutic interventions. Good cariprazine response highlights the role of dopamine dysfunction in the complex psychiatric symptoms of Rett syndrome. This can help identify the optimal treatment strategy from a transdiagnostic perspective instead of a classical diagnostic category.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Balicza, Gezsi, Fedor, Sagi, Gal, Varga and Molnar.)
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فهرسة مساهمة: Keywords: MECP2 mutation; RNA sequencing; Rett syndrome; anxiety; cariprazine; learning disability; mitochondrial dysfunction; negative symptoms
تواريخ الأحداث: Date Created: 20240122 Latest Revision: 20240123
رمز التحديث: 20240123
مُعرف محوري في PubMed: PMC10796460
DOI: 10.3389/fpsyt.2023.1301272
PMID: 38250256
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-0640
DOI:10.3389/fpsyt.2023.1301272