bims-curels 2023-01-08 papers

Issue of 2023–01–08
four papers selected by
Cure Mito Foundation

Pediatr Neurol. 2022 Dec 07. pii: S0887-8994(22)00267-3. [Epub ahead of print]140 40-46

Natural History of SURF1 Deficiency: A Retrospective Chart Review.

Tuba Rashid Khan, Inka Leprince, Souad Messahel, Berge A Minassian, Saima Kayani.

BACKGROUND: This retrospective chart review evaluated the clinical characteristics of SURF1-related neurological disease spectrum to better characterize the phenotypes.
METHODS: Patient demographics, magnetic resonance imaging abnormalities, neurological events, motor abnormalities, and gastrointestinal and respiratory assistance were evaluated in 27 patients with genetically diagnosed SURF1 deficiency.
RESULTS: The mean (S.D.) age of symptom onset collected from 13 patients was 19.7 (11.8) months. Mean (S.D.) age of diagnosis collected from 24 patients was 44.0 (45.1) months. The most common symptoms were gross motor delay (14 of 14), fine motor delay (10 of 11), verbal delay (9 of 10), and intellectual and learning disability (14 of 19). Neurological symptoms included ataxia (14 of 15), other abnormal movements (8 of 9), hypotonia (9 of 11), and dystonia (6 of 9). Three of nine reporting patients (33.3%) had a history of seizure, and 84.6% (11 of 13) had a history of regression/loss of acquired skills. Extraneurological clinical features included pulmonary complications (10 of 11) and feeding difficulties (13 of 13); cardiac complications were noted in three patients. Brainstem is frequently involved with the medulla and midbrain being the most common sites. As of July 2021, three patients were deceased.
CONCLUSIONS: The most common clinical symptoms were motor delay, verbal delay, intellectual and learning disability, dysphagia, feeding difficulties, and reflux. Neurological presentations include ataxia, hypotonia, visual/ocular abnormalities, dystonia, and imaging abnormalities include basal ganglia and brainstem lesions. Although heterogeneous, SURF1 deficiency should be considered with these clinical and imaging presentations and may support earlier identification.

Keywords: Charcot-Marie-Tooth disease 4K; Leigh syndrome; Mitochondrial disease; SURF1; SURF1 deficiency

DOI: https://doi.org/10.1016/j.pediatrneurol.2022.12.002

Am J Med Genet C Semin Med Genet. 2023 Jan 03.

Data sharing to advance gene-targeted therapies in rare diseases.

Julie Lekstrom-Himes, Erika F Augustine, Amy Brower, Thomas Defay, Richard S Finkel, Amy L McGuire, Mark W Skinner, Timothy W Yu.

Recent advancements in gene-targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long-term and transparent assessment of clinical safety and efficacy. A number of challenges will need to be addressed, including the logistical difficulties of studying rare diseases affecting individuals who may be scattered across the globe, scientific, technical, regulatory, and ethical complexities of data collection, and harmonization and integration across multiple platforms and contexts. The NCATS/NIH Gene-Targeted Therapies: Early Diagnosis and Equitable Delivery meeting series held during June 2021 included data sharing models that address these issues and framed discussions of areas that require improvement. This article describes these discussions and provides a series of considerations for future data sharing.

DOI: https://doi.org/10.1002/ajmg.c.32028

Subcell Biochem. 2023 ;102 77-98

Mitochondrial DNA Mutations and Ageing.

Julia C Whitehall, Anna L M Smith, Laura C Greaves.

Mitochondria are subcellular organelles present in most eukaryotic cells which play a significant role in numerous aspects of cell biology. These include carbohydrate and fatty acid metabolism to generate cellular energy through oxidative phosphorylation, apoptosis, cell signalling, haem biosynthesis and reactive oxygen species production. Mitochondrial dysfunction is a feature of many human ageing tissues, and since the discovery that mitochondrial DNA mutations were a major underlying cause of changes in oxidative phosphorylation capacity, it has been proposed that they have a role in human ageing. However, there is still much debate on whether mitochondrial DNA mutations play a causal role in ageing or are simply a consequence of the ageing process. This chapter describes the structure of mammalian mitochondria, and the unique features of mitochondrial genetics, and reviews the current evidence surrounding the role of mitochondrial DNA mutations in the ageing process. It then focusses on more recent discoveries regarding the role of mitochondrial dysfunction in stem cell ageing and age-related inflammation.

Keywords: Ageing; Cellular damage; DNA; Free radical damage; Mitochondria; Molecular damage; Mutations

DOI: https://doi.org/10.1007/978-3-031-21410-3_4