A Mixed-Methods Single-Case Study of Chronic Multisystem Symptoms and a DNA2 Variant
Abstract
Background
The aim of this exploratory case study (N of 1) is to examine the possible multisystem impact of mitochondrial bioenergetic vulnerability in the context of a DNA2 variant c.2565T>A (p.Asn855Lys). Limited research identifies adult-onset mitochondrial myopathy and progressive external ophthalmoplegia (PEO) as being associated with pathogenic variants in this gene. Although the specific variant in this case study is identified as a variant of uncertain significance (VUS), the longitudinal clinical picture suggests a potentially broader, pathophysiologic impact. The subject in this study is a seventy-three-year-old Caucasian female who has experienced decades of altered physiology related to multiple systems. Numerous clinical investigations were conducted; however, the root cause of these physiologic disruptions was never identified, resulting in a significant negative impact on her quality of life.
Methods
A mixed-methods, systems-based approach shapes the innovative design of this study. Of particular importance is the inclusion of the patient’s voice, through narrative symptom chronology, adding qualitative context to empirical data. Supported by scholarly literature, triangulation enhanced the validity of the findings. The author self-disclosed that she is the subject in this study, bringing rich insight as both practitioner and patient, which is often missing from traditional research. Reflexive bracketing was employed to minimize bias. The co-author contributed genetics-related content, assisted with the interpretation of genetic findings, and reviewed the thematic analysis and integration of data to support analytical rigor.
Results
Integration of narrative and empirical data yielded plausible links between reported symptoms and mitochondrial bioenergetic vulnerability across multiple physiologic systems and was supported by the literature. Functional assessments were consistent with constraints on mitochondrial bioenergetic capacity. These findings offer hypotheses in need of further exploration and are not intended to offer definitive causal relationships for this patient’s past and present symptomatology.
Conclusion
This innovative, mixed-method approach was designed to capture data that is often missed in brief clinical encounters and absent from traditional research. As genomics merges with precision and personalized medicine, this approach may offer a novel way to generate clinically meaningful hypotheses regarding the broader physiologic impact of rare genetic variants.
Keywords: DNA2, bioenergetic reserve, mixed methods, narrative medicine, case study, chronic illness, rare diseases.
Citation
Camillo, P., & Moon, D. (2026). A Mixed-Methods Single-Case Study of Chronic Multisystem Symptoms and a DNA2 Variant: Integrating Narrative and Empirical Data to Explore Possible Mitochondrial Bioenergetic Vulnerability (V 1). Zenodo. https://doi.org/10.5281/zenodo.20181427
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