Association analysis of TOR1A polymorphisms rs2296793 and rs3842225 in a Chinese population with cervical dystonia.

BACKGROUND: TOR1A (torsinA, DYT1) is the leading cause of early-onset generalized dystonia, however, the associations between common TOR1A single nucleotide polymorphisms (SNPs) and primary adult-onset focal dystonia are controversial. METHODS: In a cohort of 201 focal cervical dystonia (CD) patients, we genotyped rs2296793 and rs3842225 SNPs in TOR1A using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. We also included 289 unrelated, age- and sex-matched healthy controls (HCs) from the same region. RESULT: No significant differences were found in either the genotype distributions or minor allele frequencies (MAFs) of rs2296793 and rs3842225 between CD patients and HCs. There were no significant differences between early-onset and late-onset CD patients, between patients with and without a positive family history of dystonia, or between patients with and without tremor or sensory tricks. CONCLUSION: Our study suggests that the common rs2296793 and rs3842225 SNPs of TOR1A do not play a major role in CD in a Chinese population.

Mutations in GNAL: a novel cause of craniocervical dystonia.

IMPORTANCE: Mutations in the GNAL gene have recently been shown to cause primary torsion dystonia. The GNAL-encoded protein (Gαolf) is important for dopamine D1 receptor function and odorant signal transduction. We sequenced all 12 exons of GNAL in 461 patients from Germany, Serbia, and Japan, including 318 patients with dystonia (190 with cervical dystonia), 51 with hyposmia and Parkinson disease, and 92 with tardive dyskinesia or acute dystonic reactions. OBSERVATIONS: We identified the following two novel heterozygous putative mutations in GNAL: p.Gly213Ser in a German patient and p.Ala353Thr in a Japanese patient. These variants were predicted to be pathogenic in silico, were absent in ethnically matched control individuals, and impaired Gαolf coupling to D1 receptors in a bioluminescence energy transfer (BRET) assay. Two additional variants appeared to be benign because they behaved like wild-type samples in the BRET assay (p.Ala311Thr) or were detected in ethnically matched controls (p.Thr92Ala). Both patients with likely pathogenic mutations had craniocervical dystonia with onset in the fifth decade of life. No pathogenic mutations were detected in the patients with hyposmia and Parkinson disease, tardive dyskinesias, or acute dystonic reactions. CONCLUSIONS AND RELEVANCE: Mutations in GNAL can cause craniocervical dystonia in different ethnicities. The BRET assay may be a useful tool to support the pathogenicity of identified variants in the GNAL gene.

Minimum incidence of primary cervical dystonia in a multiethnic health care population.

BACKGROUND: The two existing estimates of the incidence of primary cervical dystonia were based on observations in relatively ethnically homogeneous populations of European descent. OBJECTIVE: To estimate the minimum incidence of primary cervical dystonia in the multiethnic membership of a health maintenance organization in Northern California. METHODS: Using a combination of electronic medical records followed by medical chart reviews, we identified incident cases of cervical dystonia first diagnosed between 1997 and 1999. RESULTS: We identified 66 incident cases of cervical dystonia from 8.2 million person-years of observation. The minimum estimate of the incidence of cervical dystonia in this population is 0.80 per 100,000 person-years. Ethnicity-specific incidence rates were calculated for individuals over age 30. Incidence was higher in white individuals (1.23 per 100,000 person-years) than in persons of other races (0.15 per 100,000 person-years, p < 0.0001). The minimum estimated incidence was 2.5 times higher in women than in men (1.14 vs 0.45 per 100,000 person-years, p = 0.0005). The average age at diagnosis was higher in women (56 years) than in men (45 years, p = 0.0004). There was no significant difference in reported symptom duration prior to diagnosis between women and men (3.9 vs 5.3 years). CONCLUSION: The estimated incidence of diagnosed cervical dystonia among white individuals in this Northern Californian population is similar to previous estimates in more ethnically homogeneous populations of largely European descent. The incidence in other races, including Hispanic, Asian, and black appears to be significantly lower. The incidence is also higher in women than in men.

[6 new cases of spasmus nutans]. / Six nouvelles observations de spasmus nutans.

Six new born presenting an acquired nystagmus, associated with rhythmic head movements, have been explored clinically, electrophysiologically and neuroradiologically. Etiopathogenic hypotheses and experimental models are proposed. A twenty last years literature review is mentioned. It seemed interesting to authors to practice head scanners to find an organic lesion. The ethnic incidence is not negligible.