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. 2025 Mar 6.
doi: 10.1111/cge.14738. Online ahead of print.

Impact of SDHA Mutations on Yeast Growth and Mitochondrial Function. Case Study Linking Genetic Findings to Clinical Phenotypes

Camilla Meossi  1 , Alessandro De Falco  1 , Marco Marchi  2 , Anna Rubegni  1 , Stefano Pagano  1 , Rosanna Trovato  1 , Claudia Nesti  1 , Flavio Dal Canto  1 , Emanuele Bartolini  1 , Leonardo Salviati  2 , Filippo Maria Santorelli  1
Affiliations

Impact of SDHA Mutations on Yeast Growth and Mitochondrial Function. Case Study Linking Genetic Findings to Clinical Phenotypes

Camilla Meossi et al. Clin Genet. .

Abstract

We present the case of a child who developed focal seizures, emotional and behavioral dysregulation, and sleep abnormalities at age 5. Trio whole genome sequencing identified biallelic mutations in the SDHA gene, which encodes a key component of mitochondrial complex II. Mitochondrial respiratory chain activities and muscle biopsy confirmed impaired oxidative metabolism. Yeast Saccharomyces cerevisiae complementation assays showed that all the mutations were presumably disease related. Mutations in SDHA are associated with developmental delay, hypotonia, ataxia, together with bilateral hyperintensities in the basal ganglia at brain MRI. This case corroborates the phenotypic variability of SDHA variants and highlights the relevance of functional assays in validating genetic findings.

Keywords: chromatinopathies; functional tests; mitochondrial respiratory chain; neurodegenerative disorders; yeast complementation.

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