Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia.

BACKGROUND: The ΔGAG deletion of the TOR1A gene (DYT1) is responsible for DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese population. METHODS: Two hundred one dystonia patients without the ΔGAG deletion were screened for other mutations in TOR1A. Gene function changes were analyzed by subcellular distribution and luciferase reporter assay. RESULTS: A novel TOR1A mutation (c.581A>T, p.Asp194Val) was found in a patient with early-onset segmental dystonia harboring a THAP1 mutation (c.539T>C, p.Leu180Ser). Overexpression of mutant TOR1A Asp194Val protein induces inclusion formation in SK-N-AS cell lines, and the repressive activity of the mutant THAP1 Leu180Ser protein on TOR1A gene expression is decreased compared with wild-type THAP1. CONCLUSIONS: This is the first report about a dystonia patient harboring two distinct dystonia gene mutations. Functional analysis indicated a potential additive effect of these two mutations, which might provoke the occurrence of dystonic symptoms in this patient.

Mutation screening of GNAL gene in patients with primary dystonia from Northeast China.

BACKGROUND: Mutations in GNAL have recently been identified as responsible for primary dystonia, however, GNAL mutations in Chinese patients with primary dystonia are not well characterized. PATIENTS AND METHODS: Fifty-nine unrelated patients with cervical onset or cervical involved primary dystonia and 120 neurologically normal controls from Northeast China without mutations of TOR1A and THAP1 were all screened for mutation of GNAL gene. RESULTS: One subject with adult-onset generalized dystonia was found have a novel nonsense GNAL mutation (c.284C>T, p.Ser95X). Another subject with adult-onset cervical dystonia was found harbor the c.932-7T>G tentative splice site mutation. Although another seventeen sequence variants were identified in both patients and controls, no disease association was found among these sequence variants. CONCLUSIONS: Mutations in GNAL gene can cause adult-onset primary dystonia in Chinese patients, and the mutation frequency is 3.4% in cervical onset or cervical involved primary dystonia. This paper identifies the first case of GNAL dystonia in the Chinese population.

Adult-onset leukoencephalopathy with brain stem and spinal cord involvement in Chinese Han population: a case report and literature review.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with an autosomal recessive mode of inheritance. We report a case of rare adult-onset LBSL with typical magnetic resonance imaging (MRI) features. The DARS2 gene mutation analysis has identified a c. 228-20_21delTTinsC (p.R76SfsX5) mutation and a c. 850G > A (p. 284E > K) mutation. With glucocorticosteroid treatment the patient has had improvement in bladder symptoms. This is the first reported adult-onset LBSL case in the Chinese Han population. A review of the literature suggests that brain lactate elevation in adult-onset LBSL is lower than early-onset cases (P < 0.01), and early-onset cases show mild intelligence and cognition decline. These observations suggest that age of onset and brain lactate levels probably influence the prognosis of LBSL.

Location of the supraorbital and infraorbital foramen with references to the soft tissue landmarks in a Chinese population.

The purpose of the current study was to determine the supraorbital foramen (SOF) and infraorbital foramen (IOF) based on soft tissue landmarks, to facilitate prediction of the location of this structure during facial surgery. Forty-two hemispheres of 21 adult cadavers (16 men and 5 women; aged 30-75 years) were dissected to expose the SOF and IOF. The locations of the SOF and IOF were evaluated with direct and photographic measurements. The data gained were analyzed by statistical method. The SOF localized 23.11 ± 2.35 mm superior and 9.48 ± 3.06 mm lateral to the angulus oculi medialis (AOM). The vertical angle from AOM to SOF was 68.3 (SD, 6.44) degrees. The SOF localized 24.81 (SD, 3.39) mm inferior and 10.89 (SD, 2.78) mm lateral to the AOM on the front view. The vertical angle from AOM to IOF was 66.5 (SD, 5.18) degrees. The SOF localized 11.22 (SD, 2.01) mm inferior and 6.09 (SD, 2.32) mm lateral to the ala of the nose (AL) on the front view. The vertical angle from AL to IOF was 61.7 (SD, 7.61) degrees. These results were a little different from the results of some other populations. We found the IOFs located on the point of one-fifth proportion distant to the ALs along the vertical direction distance from AL to SOF, whereas the AOMs located on the point of three-fifths proportion distant from the AL. Our results may provide more detailed information to predict the location of the SOFs and IOFs and help to prevent nerve or vessel damage.

Subcellular distribution of THAP1 and alterations in the microstructure of brain white matter in DYT6 dystonia.

BACKGROUND: Mutations in the THAP1 gene have recently been identified as the cause of DYT6 primary dystonia. However, the changes in THAP1 gene function and in the microstructure of brain white matter have not been well-characterized. METHODS: Four different mutations of THAP1 expression (clones F22fs71X, C54F, F25fs53X, and L180S) were transfected into HEK-293T cells. The subcellular distribution of THAP1 in each clone was identified using immunofluorescence microscopy and Western blot. Six patients who harbored these THAP1 mutations underwent diffusion tensor magnetic resonance imaging (DTI) of the brain. The fractional anisotropy (FA) and mean diffusivity (MD) were measured in twenty-four regions of interest (ROI). RESULTS: In two truncated mutations (F22fs71X and F25fs53X), the subcellular distribution of THAP1 were both in the cytoplasm and nucleus. However, the subcellular distribution was detected almost in the nucleus in two missense mutations (C54F and L180S). In the DTI maps, the average values of fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of the DYT1 carriers, comparing with controls. CONCLUSIONS: Truncated THAP1 mutations (F22fs71X and F25fs53X) can alter the subcellular distributions, while some missense mutation (C54F and L180S) can not. The axonal integrity and coherence in the region of sensorimotor area of the brain was damaged in DYT6 dystonia.

Morphological analysis of the vertebral and basilar arteries in the Chinese population provides greater diagnostic accuracy of vertebrobasilar dolichoectasia and reveals gender differences.

PURPOSE: Previous studies suggest that cerebral artery diameter and position differ with both gender and ethnicity, making diagnosis of vertebrobasilar dolichoectasia (VBD) difficult. Thus, the current study investigated the morphology and potential gender differences of the vertebral (VA) and basilar arteries (BA) in the Chinese population. The data collected also enabled some criteria to be suggested for the diagnosis of VBD by MRI. METHODS: A total of 200 healthy participants who underwent magnetic resonance imaging (MRI) were enrolled. The diameters of the BA and VA were measured using high resolution MRI and the height of the basilar artery bifurcation and the position of the basilar artery were also analyzed. The 95 % confident intervals (CI) of vessel diameter were calculated. RESULTS: The diameters of each artery measured, significantly differed with gender (p < 0.01). The 95 % CI of the BA were 2.2-4.2 mm and 2.0-4.0 mm for males and females, respectively. The 95 % CI of the VA were 1.7-3.7 mm and 1.5-3.5 mm for males, and 1.4-3.4 mm and 1.1-3.1 mm for females for the left and right side, respectively. No significant gender difference was found in height of the BA bifurcation or the position of the BA. CONCLUSIONS: There are significant gender differences in the diameter of both the VA and BA, indicating that gender needs to be considered in the diagnosis of VBD. These results also provide much needed quantitative data for the diagnosis of VBD in Chinese people.

Sex assessment using measurements of the first lumbar vertebra.

Sex determination is a vital part of the medico-legal system but can be difficult in cases where the integrity of the body has been compromised. The purpose of this study was to develop a technique for sex assessment from measurements of the first lumber vertebrate. Twenty-nine linear measurements and five ratios were collected from 113 Chinese adult males and 97 Chinese adult females using digital three-dimensional anthropometry methods. By using discriminant analysis, we found that 23 linear measurements and two ratios identified sexual dimorphism (P<0.01), with predictive accuracy ranging from 57.1% to 86.6%. Using a stepwise method of discriminant function analysis, we found three dimensions predicted sex with 88.6% accuracy: (a) upper end-plate width (EPWu), (b) left pedicle height (PHl), and (c) middle end-plate depth (EPDm). This study shows that a single first lumber vertebra can be used for this purpose, and that the discriminant equation will help forensic determination of sex in the Chinese population.

THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.

Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.

Use of anthropometric data from the medial tibial and femoral condyles to design unicondylar knee prostheses in the Chinese population.

Anthropometric data on medial tibial condyles and medial femoral condyles of 172 normal knees (94 male knees, 78 female knees) were obtained using three-dimensional computer tomographic measurements. In the medial tibial condyle, we measured the anteroposterior (AP) and widest dimension (WD), and compared the measurements with the similar dimensions of five tibial unicondylar knee prostheses conventionally used in China. In the femur, we used best-fit two-circular arcs to measure the morphology of the sagittal plane of the medial femoral condyle. We found that three of the prostheses showed WD overhang for all ranges of the AP dimension, while two of them showed WD underhang. We also found a progressive decrease in the condylar aspect ratio (WD/AP%) in parallel with an increase in the AP dimension in the medial tibial condyle. However, none of the conventional tibial prosthesis showed a similar change. Furthermore, males had larger values in aspect ratio than females with the same values for AP dimension. There were definite correlations between the radius of the curvature for the posterior part (R1) and distal part (R2) in the sagittal plane of medial femoral condyle. Both of these values were smaller than in the Caucasian population. Both radiuses of curvature for the posterior and distal components showed definite correlations with the AP dimension. The results of this study may provide guidelines for designing unicondylar knee prostheses suitable for the Chinese population.

Location of mental foramen based on soft- and hard-tissue landmarks in a chinese population.

The purpose of the present study was to determine the location of the mental foramen (MF) based on soft- and hard-tissue landmarks, to facilitate prediction of the location of this structure during facial and dental surgery. Forty-two hemispheres of 21 adult cadavers (16 men and 5 women; aged 30-75 years) were dissected to expose the MF. The locations of the MFs were evaluated with direct and photographic measurements. Most of the MFs presented a single foramen (95%), except for only 2 cases with double foramina (5%). The MFs localized 23.38 +/- 2.00 mm inferior and 3.55 +/- 1.70 mm medial to the cheilion in the front view while 23.59 +/- 2.11 mm inferior and 7.19 +/- 3.03 mm posterior to the cheilion in the lateral view. Based on the hard-tissue landmarks, we found that most of the MFs localized inferior the second premolar in most of the cases (73.8%), and the MFs localized 23.34 +/- 2.39 mm below the cusp tip of the second premolar, 16.56 +/- 2.53 mm below the inferior alveoli, and 15.56 +/- 1.74 mm superior the bottom of the mandible. The position of the MF varied from 8.7 degrees medial to 15.5 degrees posterior in the vertical angle with the change of surgical body position from supine to lay-side position. Our results may provide a more detailed information to predict the location of the MFs.

Three dimensional morphometry of the knee to design the total knee arthroplasty for Chinese population.

Anthropometric data on the proximal tibia and distal femur of 172 normal knees (94 male knees, 78 female knees) were obtained using three dimensional computer tomographic measurements. We measured the tibial mediolateral (tML) and tibial anteroposterior (tAP) dimension in resected proximal tibia surface, femoral mediolateral (fML) and femoral anteroposterior (fAP) dimension in resected distal femur surface. The measurements were compared with the similar dimensions of five total knee prostheses conventionally used in China. We found that in the smaller sized prostheses the tibial mediolateral dimension was undersized, while in the larger size prostheses the tibial mediolateral dimension was overhang. For all sizes of prostheses the femoral mediolateral dimension was overhang. We found a progressively decreased in the aspect ratio (ML/AP %) with an increasing anteroposterior dimension both in the tibia and femur, as compared to the constant aspect ratio shown by the conventional total prostheses. Male had larger values in mediolateral dimension and aspect ratio than female under a given anteroposterior dimension both in the tibia and femur. There were strong correlations between measurements of the tibia and femur. The results of this study may provide guidelines for designing suitable total knee prosthesis for the Chinese population, especially for design of gender-specific prostheses.