A number sign (#) is used with this entry because of evidence that dystonia-31 (DYT31) is caused by homozygous or compound heterozygous mutation in the AOPEP gene (619600) on chromosome 9q22.

Dystonia-31 (DYT31) is an autosomal recessive progressive neurologic disorder characterized by involuntary muscle twisting movements and postural abnormalities affecting the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties. The age at onset ranges from childhood to young adulthood. There are usually no additional neurologic symptoms, although late-onset parkinsonism was reported in 1 family (summary by Zech et al., 2022).

Zech et al. (2022) reported 5 patients from 4 unrelated families of European origin with DYT31. The patients, who were ascertained through online matchmaking platforms, ranged in age from 52 to 61 years, except for 1 patient who was 13 years old. The age at symptom onset ranged from 9 to 36 years. The dystonia was either multifocal or generalized. All affected individuals had upper limb involvement, manifest as writer's cramp, and most also had neck, face, trunk, and lower limb involvement causing walking difficulties. The disorder was progressive. At least 1 patient required a wheelchair due to significant torticollis. Other features included speech articulation difficulties, muscle cramping and pain, orofacial dyskinesia, and swallowing dysfunction. None had tremor. Two sibs in 1 French family (family 4) developed late-onset parkinsonism with akinesia, frequent falls, bradykinesia, and dysarthria. Brain imaging and laboratory studies were unremarkable.

The transmission pattern of DYT31 in the families reported by Zech et al. (2022) was consistent with autosomal recessive inheritance.

In 5 patients from 4 unrelated families with DYT31, Zech et al. (2022) identified homozygous or compound heterozygous nonsense, splice site, or frameshift mutations in the AOPEP gene (see, e.g., 619600.0001-619600.0005). The mutations, which were found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. None were present in the homozygous state in gnomAD. Functional studies of the variants were not performed, but all were predicted to cause nonsense-mediated mRNA decay and a loss of function. Zech et al. (2022) noted that AOPEP is expressed in the developing and adult human brain and belongs to a family of proteolytic enzymes implicated in synaptogenesis and neuronal maintenance.