SNOMEDCT: 783179009; ORPHA: 420485; DO: 0090052;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p14.3-p14.2 | Dystonia 24 | 615034 | Autosomal dominant | 3 | ANO3 | 610110 |
A number sign (#) is used with this entry because dystonia-24 (DYT24) is caused by heterozygous mutation in the ANO3 gene (610110) on chromosome 11p14.
Dystonia-24 is an autosomal dominant form of focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs (summary by Charlesworth et al., 2012).
Munchau et al. (2000) reported a British family in which 5 individuals had craniocervical dystonia. The mean age at onset was 29 years (range, 19 to 40). Another individual was possibly affected. All patients had jerky cervical dystonia; other variable features included blepharospasm, voice tremor, writing tremor, head tremor, and arm tremor. Four had dystonic arm posturing.
Charlesworth et al. (2012) reported 3 additional unrelated patients with dystonia. Most patients had adult-onset of cervical dystonia, often with laryngeal involvement and tremor of the upper limb. One patient had onset in the first decade of life, and another had oromandibular dystonia.
The transmission pattern of dystonia in the family reported by Munchau et al. (2000) was consistent with autosomal dominant inheritance.
In affected members of a British family with autosomal dominant dystonia-24 reported by Munchau et al. (2000), Charlesworth et al. (2012) identified a heterozygous mutation in the ANO3 gene (R494W; 610110.0001). The mutation, which was identified by linkage analysis combined with exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in this family and was not found in several large control exome databases. A different heterozygous mutation (W490C; 610110.0002) was subsequently identified in affected members of another family with autosomal dominant cervical dystonia. High-throughput sequencing of this gene in 188 samples yielded 4 additional putative pathogenic variants (see, e.g., 610110.0003-610110.0004). Patient fibroblasts with the W490C mutation showed a defect in endoplasmic reticulum-related calcium handling. Charlesworth et al. (2012) postulated that mutations in the ANO3 gene may lead to abnormal striatal-neuron excitability, manifest as dystonia.
Although Charlesworth et al. (2012) referred to this disorder as dystonia-23 (DYT23), that designation had already been used to refer to a dystonia locus on chromosome 9q34 (614860). Thus, dystonia caused by mutation in the ANO3 gene on chromosome 11p14 is referred to here as DYT24.
Charlesworth, G., Plagnol, V., Holmstrom, K. M., Bras, J., Sheerin, U.-M., Preza, E., Rubio-Agusti, I., Ryten, M., Schneider, S. A., Stamelou, M., Trabzuni, D., Abramov, A. Y., Bhatia, K. P., Wood, N. W. Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis. Am. J. Hum. Genet. 91: 1041-1050, 2012. [PubMed: 23200863] [Full Text: https://doi.org/10.1016/j.ajhg.2012.10.024]
Munchau, A., Valente, E. M., Davis, M. B., Stinton, V., Wood, N. W., Quinn, N. P., Bhatia, K. P. A Yorkshire family with adult-onset cranio-cervical primary torsion dystonia. Mov. Disord. 15: 954-959, 2000. [PubMed: 11009204] [Full Text: https://doi.org/10.1002/1531-8257(200009)15:5<954::aid-mds1028>3.0.co;2-i]