Digenic inheritance of mutations in SPG7 and AFG3L2 causes late-onset ataxia with pyramidal signs - Takeaways - MDSpire

Combined SPG7 and AFG3L2 Mutations Are Associated with Late-Onset Ataxia and Pyramidal Signs

By
Efthymia Kafantari
Sorina Gorcenco
Andreas Puschmann
November 12, 2026

Bmc Medicine

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1

The patient had heterozygous variants in SPG7 and AFG3L2, supporting a digenic cause of late-onset ataxia.
2

Ataxia began at approximately 45 years, with predominantly lower-limb cerebellar signs and hyperreflexia after 13 years of disease.
3

The SPG7 splice-site deletion was predicted to cause aberrant splicing and a partial in-frame deletion of 3 amino acids.
4

The AFG3L2 p.(Arg702Gln) variant was rare and had also been reported in a French family with the same digenic genotype.
5

Follow-up showed ptosis, progressive oculomotor dysfunction, orthostatic hypotension, and a variable, slowly progressive course.

Original Source(s)

Bmc Medicine

Digenic inheritance of mutations in SPG7 and AFG3L2 causes late-onset ataxia with pyramidal signs

by Efthymia Kafantari, Sorina Gorcenco, Andreas Puschmann
November 12, 2026

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