Our patient and three other reported carriers of non-c.907_909delGAG-mutations within the first three exons of TOR1A showed similar phenotypes of adult-onset focal or segmental cervical dystonia.
Analysis of 83 published series including 5,057 patients indicated significant differences in the mean age at onset of five phenotypes of PTD (mean age at onset; 95% CI): DYT1 dystonia (11.3 years; 10.3 to 12.2), writer's cramp (38.4; 36.9 to 39.9), CD (40.8; 40.3 to 41.3), spasmodic dysphonia (43.0; 42.2 to 43.9), and blepharospasm-oromandibular dystonia (55.7; 55.1 to 56.4).
We explored the influence of the Val66Met SNP of the BDNF gene on the risk of cranial and cervical dystonia in a cohort of 156 Italian patients and 170 age- and gender-matched healthy control subjects drawn from the same population.
Adult-onset idiopathic focal dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp), is mostly associated with the DYT7 locus, which was originally mapped to chromosome 18p by genomewide linkage analysis in a large family showing autosomal dominant inheritance.
Recent genetic studies suggest that the Val66Met polymorphism of the BDNF gene is a genetic modifier in cranial-cervical dystonia in Caucasians.However, the finding is not consistent.
Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD.
One novel likely pathogenic substitution (c.1061T>C; p.Val354Ala) in GNAL was detected in a sporadic cervical dystonia patient (mutation frequency: 0.4%).
Mutations in GNAL have been associated with adult-onset cranio-cervical dystonia, but a limited number of cases have been reported so far and the clinical spectrum associated with this gene still needs to be fully characterized.
In addition, splicing variants of CIZ1 mRNA is associated with a variety of cancers and Alzheimer's disease, and mutations of the CIZ1 gene lead to cervical dystonia.
The one family who was the exception had two gene positive members of DRD and one with dopa-unresponsive cervical dystonia with negative GCH1 mutation.
A case-control allelic association study is described of 100 patients with cervical dystonia and 100 controls using polymorphisms within D1-5 receptor and dopamine transporter genes.
Subsequent screening of these candidate causal variants in a large number of familial and sporadic cases of cervical dystonia led to the identification of a total of six putatively pathogenic mutations in ANO3, a gene encoding a predicted Ca(2+)-gated chloride channel that we show to be highly expressed in the striatum.
However, by combining results with other studies on BoNT/A-treated Caucasian patients with cervical dystonia (CD), we found that, among Caucasian patients treated with BoNT/A, DQA1*01:02 and DQB1*06:04 were higher in Ab-positive than in Ab-negative patients.
A potentially pathogenic rare 3bp-in-frame deletion was found in a patient with cervical dystonia but no copy number variations were detected in this study, suggesting that TUBB4A mutations exceedingly rarely contribute to the etiology of isolated dystonia.
Recently, ATM mutations have been found in 13 Canadian Mennonites with early-onset, isolated, predominantly cervical dystonia, in a French family with generalized dystonia and in an Indian family with dopa-responsive cervical dystonia.
The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region.
Current study suggests that NMS are prevalent in Chinese CD and BSP patients, and the motor severity of dystonia did not contribute to the severity of nonmotor symptoms.