Neurology. Genetics · 2026
Compound Heterozygous COA7 Variants Presenting With Childhood-Onset Axonal Neuropathy in 2 Siblings.
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Cicala Gianpaolo, Rolleri Elisa, Berti Beatrice, Luigetti Marco, Forcina Nicola, Villa Marianna, Capasso Anna, Arpaia Chiara, Malaspina Martina, Fattori Fabiana, Bosco Luca, Primiano Guido, Novelli Antonio, Rizza Teresa, Bertini Enrico, Pane Marika, Mercuri Eugenio
Аннотация
OBJECTIVES: Variants in COA7 (cytochrome c oxidase assembly factor 7) are a rare cause of mitochondrial disease, with limited clinical descriptions and phenotypic variability. We describe 2 siblings carrying compound heterozygous COA7 variants, one of which (c.457C>T; p.Leu153Phe) is novel. Both presented with early-onset, slowly progressive axonal sensorimotor neuropathy, with differences in severity and associated features.
METHODS: Patients were identified based on clinical presentation and evaluated through longitudinal neurologic, neurophysiologic, genetic, biochemical, and neuroimaging assessments.
RESULTS: The elder brother developed symptoms at age 12, including muscle cramps, tremors, and falls, whereas the sister showed motor impairment with difficulty walking and running from age 5, along with more prominent cerebellar involvement. Shared features included distal weakness, impaired gait, areflexia, tremor, pes cavus, sensory disturbances, and cognitive difficulties, which were milder in the older brother. Nerve conduction studies demonstrated axonal sensorimotor polyneuropathy. Genetic analysis identified 2 compound heterozygous COA7 variants. Skin biopsy revealed reduced mitochondrial complex IV activity. Brain MRI findings were unremarkable in both siblings.
DISCUSSION: These cases expand the clinical spectrum of COA7-related disorders and illustrate the potential for intrafamilial phenotypic variability. The identification of a novel variant and extended clinical follow-up provide further insight into the features associated with COA7 variants.
METHODS: Patients were identified based on clinical presentation and evaluated through longitudinal neurologic, neurophysiologic, genetic, biochemical, and neuroimaging assessments.
RESULTS: The elder brother developed symptoms at age 12, including muscle cramps, tremors, and falls, whereas the sister showed motor impairment with difficulty walking and running from age 5, along with more prominent cerebellar involvement. Shared features included distal weakness, impaired gait, areflexia, tremor, pes cavus, sensory disturbances, and cognitive difficulties, which were milder in the older brother. Nerve conduction studies demonstrated axonal sensorimotor polyneuropathy. Genetic analysis identified 2 compound heterozygous COA7 variants. Skin biopsy revealed reduced mitochondrial complex IV activity. Brain MRI findings were unremarkable in both siblings.
DISCUSSION: These cases expand the clinical spectrum of COA7-related disorders and illustrate the potential for intrafamilial phenotypic variability. The identification of a novel variant and extended clinical follow-up provide further insight into the features associated with COA7 variants.