Clinical Features, <b><i>DYT1</i></b> Mutation Screening and Genotype-Phenotype Correlation in Patients with Dystonia from Iran

Abstract

Objective: To test Iranian patients with primary torsion dystonia to determine the frequency of 904–906 del GAG mutation in the DYT1 (TOR1A) gene and to investigate the genotype-phenotype association for this disease. Subjects and Methods: Sixty-three patients with primary dystonia were investigated. DNA was extracted from peripheral blood and these samples were subjected to PCR-sequencing for exon 5 of the DYT1 gene. Results: Of the 63 patients, 10 (15.9%) carried the triplet GAG deletion mutation; this is a high DYT1-positive rate in comparison with other populations and the type of dystonia in this positive group was generalized in all except 1. In our patients, limbs were the most severely involved site at the time of onset and in most cases it developed to generalized form. The majority of DYT1-positive cases showed higher leg onset (5 patients, 62.5%) in comparison with higher arm onset in negative patients (20 patients, 50%). Also, the progression to generalized dystonia in DYT1-positive patients was significantly higher than in DYT1-negative patients. The mean age at onset was 8.6 ± 1.6 years (7–12 years) in DYT1-positive patients, while mean age at onset in patients with no GAG deletion mutation was higher (15.7 ± 11.5 years). Conclusions: The DYT1 904–906 del GAG mutation is responsible for some of Iranian dystonia patients, and screening for the DYT1 deletion is significant in cases with the generalized type of primary dystonia. Also, patients with leg or arm onset at a younger age are more likely to be DYT1-positive among primary torsion dystonia cases.

TorsinB overexpression prevents abnormal twisting in DYT1 dystonia mouse models

“…DYT1 dystonia is a dominantly inherited movement disorder that is caused by 3-bp in-frame deletion (DE mutation) in the TOR1A gene that encodes the torsinA protein [1]. Only ~30% of mutation carriers exhibit symptoms, which vary in severity from mild to severely debilitating [2,3]. Treatments include deep brain stimulation, which is invasive, and anticholinergic drugs, which provide incomplete relief and are plagued by side effects [4,5].…”

NewTHAP1mutation and role of putative modifier inTOR1A

“…There are marked phenotypic variability and a 30% reduced penetrance. Initially thought to affect around 60% of non‐Jewish patients with generalized dystonia, later reports showed a lower prevalence in other areas . Conversely, DYT6 also has an early onset, but with frequent craniocervical or arm involvement, with secondary generalization .…”

Primary generalized dystonia due to TOR1A ΔGAG mutation in an Indian family with intrafamilial clinical heterogeneity

“…A trinucleotide deletion (∆GAG) in TOR1A gene has been reported to be the most common cause of PTD (DYT1) in various populations. [2][3][4][5] This mutation was found to be more common in Ashkenazi Jew patients though it was found in most of the world dystonia cohorts. DYT1 dystonia is an autosomal dominant primary dystonia with a reduced penetrance (30%-40%).…”

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late-onset leukodystrophy phenotype. [5] Genetic testing could not be done in other family members.In conclusion, special attention should be paid to the radiologic findings of the cases with late-onset leukodystrophy in which biochemical and metabolic screening tests give unremarkable results. AARS2 gene mutation should then be considered in the differential diagnosis.

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