Early onset dystonia
Gene: ARX
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant.
- Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021
Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI.
- Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021
Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers.
- Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021
Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out.
- Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021Created: 6 Dec 2021, 6:51 a.m. | Last Modified: 6 Dec 2021, 6:51 a.m.
Panel Version: 1.99
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications
Gene: arx has been classified as Green List (High Evidence).
Phenotypes for gene: ARX were changed from Dystonia to Developmental and epileptic encephalopathy 1, OMIM:308350; X-linked spasticity-intellectual disability-epilepsy syndromeMONDO:0017856; Partington syndrome, OMIM:309510; Partington syndrome, MONDO:0010654
Publications for gene: ARX were set to
17th Oct 2016: Promoted to version 1. The panel was revised after expert input and internal discussion with the clinical team. Other panels such as hereditary ataxia or dementia may be applied in conjunction with this panel where appropriate for genome analysis.
ARX was added to Early onset dystoniapanel. Sources: Emory Genetics Laboratory