Dystonia, chorea or related movement disorder, childhood onset

Gene: C9orf3

Green List (high evidence)

Zech et al. (2022) reported five affected individuals from four unrelated families with biallelic AOPEP variants and overlapping phenotypes of disabling, progressive dystonia predominantly affecting the upper and lower limbs, with variable craniocervical involvement. Dystonia was isolated in three families; the two affected siblings in the fourth family also developed late-onset parkinsonism. Seven distinct variants were identified: three nonsense, three frameshift and one splice-site variant. One individual was homozygous and the remaining four were compound heterozygous. These findings support an autosomal recessive gene–disease association. AOPEP encodes a zinc-dependent aminopeptidase expressed in the developing and adult brain. The genetic findings support loss of function as the proposed mechanism, although the splice variant produces in-frame deletions and its effect on protein function was not directly demonstrated.

Note on nomenclature: C9orf3 is known as AOPEP.
Sources: Literature

Created: 26 Oct 2026, 10:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 34596301