A novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients. Three reported mutations (IVS2-2A>G, c.293C>T, c.550C>T) were detected in GCH1, whereas two compound heterozygous variants were identified in TH, one of which was novel (c.1083C>A). Furthermore, this novel variant was not detected in any of the 250 ethnicity-matched, healthy controls. No exon deletions or duplicate mutations in the two genes were found in patients with DRD. No mutation in SPR was found. In addition, one patient with the IVS2-2A>G mutation in GCH1 showed signs of Parkinsonism. In conclusion, we here identified a novel heterozygous variant in TH (c.1083C>A). It is important to perform routine screening of GCH1 and TH for patients with DRD. While for patients with Parkinsonism, GCH1 mutation analysis should be performed after screening of genes like PARKIN, PARK7 (DJ-1) and PINK1.

Fine mapping and whole-exome sequencing of a familial cortical myoclonic tremor with epilepsy family.

Familial cortical myoclonic tremor with epilepsy (FCMTE) is an autosomal dominant epilepsy syndrome. Four loci, including 8q24 (FCMTE1), 2p11.1-q12.2 (FCMTE2), 5p15.31-p15.1 (FCMTE3), and 3q26.32-3q28 (FCMTE4) were previously reported. Herein, we report a new FCMTE1 pedigree from Chinese population with its clinical and genetic study results. Whole genome scan was performed to identify the causative gene region and copy number variants. Whole-exome sequencing was used to identify the causative gene. There were twelve affected members alive in this FCMTE1 pedigree. Nine affected members had both cortical myoclonic tremor and epilepsy, while three affected members had only cortical myoclonic tremor. Electrophysiologic examinations manifested giant somatosensory evoked potentials and long-latency cortical reflex in some affected members. Whole genome scan identified a 20.4 Mb causative gene region at 8q22.3-q24.13. No copy number variants were identified as the causative mutation. Whole-exome sequencing identified a co-segregated mutation (c.206A>T; p.Y69F) in the SLC30A8 gene. However, the evidence supporting this gene as the causative gene of FCMTE1 is not enough. We report the first Chinese FCMTE1 pedigree. No copy number variants, point mutation or small insertion/deletion were detected in the identified region that showed an association with FCMTE1. Further studies could focus on other possible genetic mechanisms while the association between the SLC30A8 and FCMTE1 needs further evidence.

Mills' syndrome is a unique entity of upper motor neuron disease with N-shaped progression: Three case reports.

BACKGROUND: Mills' syndrome is an extremely rare degenerative motor neuron disorder first described by Mills in 1900, but its nosological status is still not clear. We aimed to analyze the clinical features of Mills' syndrome. CASE SUMMARY: Herein, we present 3 cases with similar features as those described in Mills' original paper and review the related literature. Our patients showed middle- and older-age onset, with only upper motor neuron symptoms evident throughout the course of the disease. Spastic hemiplegia began in the lower extremity with a unique progressive pattern. CONCLUSION: We consider that Mills' syndrome is a unique entity of motor neuron disorder with an N-shaped progression. Clinicians should maintain a high index of suspicion for the diagnosis of Mills' syndrome when the onset involves lower extremity paralysis without evidence of lower motor neuron or sensory involvement.

Congenital anomaly of the posterior arch of the atlas: a rare risk factor for posterior circulation stroke.

We report an extremely rare case involving a posterior arch anomaly of the atlas, causing a vertebral artery dissection (VAD) induced posterior circulation stroke. A 16-year-old girl was admitted to hospital because of new onset dizziness. VAD related multiple infarction in the posterior circulation was revealed. The congenital posterior arch anomaly of the atlas, along with instability of the atlantoaxial joint, were discovered accidentally during follow-up. This is the first case of ischemic stroke related to atlantal posterior arch aplasia and atlantoaxial instability. Although rare, it reminds us that investigation of the craniovertebral junction should be considered when stroke occurs in young patients.

Congenital anomaly of the posterior arch of the atlas: a rare risk factor for posterior circulation stroke.

We report an extremely rare case involving a posterior arch anomaly of the atlas, causing a vertebral artery dissection (VAD) induced posterior circulation stroke. A 16-year-old girl was admitted to hospital because of new onset dizziness. VAD related multiple infarction in the posterior circulation was revealed. The congenital posterior arch anomaly of the atlas, along with instability of the atlantoaxial joint, were discovered accidentally during follow-up. This is the first case of ischemic stroke related to atlantal posterior arch aplasia and atlantoaxial instability. Although rare, it reminds us that investigation of the craniovertebral junction should be considered when stroke occurs in young patients.

Validity and reliability testing of the Chinese (mainland) version of the 39-item Parkinson's Disease Questionnaire (PDQ-39).

The 39-item Parkinson's Disease Questionnaire (PDQ-39) has been tested in many languages, but not in Chinese mainland. We aimed to assess the Chinese (mainland) version of the PDQ-39. Seventy-one subjects with Parkinson's disease (PD) completed the PDQ-39 and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). All subjects were retested with the PDQ-39 a week later. The united Parkinson's disease rating scale (UPDRS) and the Hoehn and Yahr (H & Y) scale were also used to evaluate the subjects. Reliability was assessed by Cronbach's alpha and intra-class correlation coefficient (ICC). Validity was examined in terms of agreement with SF-36, UPDRS, and H & Y scales. The Chinese (mainland) version of the PDQ-39 demonstrated acceptable reliability (Cronbach's alpha: 0.84-0.88; ICC: 0.56-0.82). The item-total correlations (0.33-0.88) and scaling success rates (77.56%) indicated satisfactory convergent and discriminant validity of the PDQ-39 items. The correlations between related constructs of the PDQ-39 and UPDRS (r=0.44-0.68) and between those of the PDQ-39 and SF-36 (r=(-0.46)-(-0.69)) were all statistically significant (P<0.01). Except for stigma, cognitions, and bodily discomfort, all other dimensions of the PDQ-39 significantly discriminated patients at different H & Y stages indicated by the H & Y scale. Although our observations indicate that some problematic subscales of this version of the PDQ-39 could be improved upon, this study suggests acceptable reliability and validity of the Chinese (mainland) version of the PDQ-39.