scholarly journals GGC Repeat Expansion in the NOTCH2NLC Gene Is Associated With a Phenotype of Predominant Motor–Sensory and Autonomic Neuropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Wang ◽  
Jiaxi Yu ◽  
Meng Yu ◽  
Jianwen Deng ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Autonomic Neuropathy ◽  
Repeat Expansion ◽  
Lower Limbs ◽  
Chinese Patients ◽  
Muscle Pathology ◽  
Considerable Proportion ◽  
Causative Gene ◽  
Mainland Chinese ◽  
Repeat Size

There is still a considerable proportion of patients with inherited peripheral neuropathy (IPN) whose pathogenic genes are unknown. This study was intended to investigate whether the GGC repeat expansion in the NOTCH2NLC is presented in some patients with IPN. A total of 142 unrelated mainland Chinese patients with highly suspected diagnosis of IPN without any known causative gene were recruited. Repeat-primed polymerase chain reaction (RP-PCR) was performed to screen GGC repeat expansion in NOTCH2NLC, followed by fluorescence amplicon length analysis-PCR (AL-PCR) to determine the GGC repeat size. Detailed clinical data as well as nerve, muscle, and skin biopsy were reviewed and analyzed in the NOTCH2NLC-related IPN patients. In total, five of the 142 patients (3.52%) were found to have pathogenic GGC expansion in NOTCH2NLC, with repeat size ranging from 126 to 206 repeats. All the NOTCH2NLC-related IPN patients presented with adult-onset motor–sensory and autonomic neuropathy that predominantly affected the motor component of peripheral nerves. While tremor and irritating dry cough were noted in four-fifths of the patients, no other signs of the central nervous system were presented. Electrophysiological studies revealed both demyelinating and axonal changes of polyneuropathy that were more severe in lower limbs and asymmetrically in upper limbs. Sural nerve pathology was characterized by multiple fibers with thin myelination, indicating a predominant demyelinating process. Muscle pathology was consistent with neuropathic changes. P62-positive intranuclear inclusions were observed in nerve, skin, and muscle tissues. Our study has demonstrated that GGC expansion in NOTCH2NLC is associated with IPN presenting as predominant motor–sensory and autonomic neuropathy, which expands the phenotype of the NOTCH2NLC-related repeat expansion spectrum. Screening of GGC repeat expansions in the NOTCH2NLC should be considered in patients presenting with peripheral neuropathy with tremor and irritating dry cough.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients

2021 ◽  
Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Radical Nephroureterectomy ◽  
Ki 67 ◽  
Data Set ◽  
Mainland Chinese ◽  
Upper Tract

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients

2014 ◽  
Vol 59 (5) ◽  
pp. 256-261 ◽  
Author(s):  
Min Zhu ◽  
Xuan Zhu ◽  
Xueliang Qi ◽  
Ding Weijiang ◽  
Yajing Yu ◽  
...  
Keyword(s):  
Literature Review ◽  
Chinese Patients ◽  
Mainland Chinese

scholarly journals Prevalent Pathogenic Variants of ATP7B in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 336
Author(s):  
Guo-Min Yang ◽  
Rou-Min Wang ◽  
Nan Xia ◽  
Zi-Wei Zheng ◽  
Yi Dong ◽  
...  
Keyword(s):  
Geographical Distribution ◽  
Founder Effect ◽  
Wilson’S Disease ◽  
Autosomal Recessive Disorder ◽  
Wilson's Disease ◽  
Chinese Patients ◽  
Mainland Chinese ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
The Common

Wilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the ATP7B gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (p < 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.

scholarly journals Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hai-Lin Dong ◽  
Jia-Qi Li ◽  
Gong-Lu Liu ◽  
Hao Yu ◽  
Zhi-Ying Wu
Keyword(s):  
Ex Vivo ◽  
Protein Solubility ◽  
Chinese Patients ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Causative Gene ◽  
Hereditary Motor ◽  
Functional Studies ◽  
Hereditary Motor Neuropathy

AbstractSorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot–Marie–Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.

A variant of the gene HARS detected in the clinical exome: etiology of a peripheral neuropathy undiagnosed for 20 years

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Raquel Lahoz Alonso ◽  
Paula Sienes Bailo ◽  
Jose Luis Capablo Liesa ◽  
Sara Álvarez de Andrés ◽  
Jose Luis Bancalero Flores ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Neurological Disease ◽  
Motor Impairment ◽  
Lower Limbs ◽  
Case Presentation ◽  
Genetic Sequencing ◽  
Charcot Marie Tooth ◽  
Sensory Motor ◽  
Exacerbation Of Symptoms ◽  
Over Time

AbstractObjectivesDescribe a case with axonal Charcot-Marie-Tooth (CMT) type 2W, a neurological disease characterized by peripheral neuropathy typically involving the lower limbs and causing gait alterations and distal sensory-motor impairment.Case presentationWe report this case, where the application of massive genetic sequencing (NGS) with clinical exome in a molecular genetics laboratory enabled to detect the presence of candidate variants of the clinic of the patient.ConclusionsThe variant detected in HARS gene suggests that this variant could be causative of the symptoms of the patient, who went undiagnosed for 20 years and experienced an exacerbation of symptoms over time.

scholarly journals The clinical and genetic features in a cohort of mainland Chinese patients with thyrotoxic periodic paralysis

BMC Neurology ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiaobing Li ◽  
Sheng Yao ◽  
Yining Xiang ◽  
Xiaolei Zhang ◽  
Xiangbing Wu ◽  
...  
Keyword(s):  
Periodic Paralysis ◽  
Chinese Patients ◽  
Thyrotoxic Periodic Paralysis ◽  
Mainland Chinese ◽  
Genetic Features

Neuronal intranuclear hyaline inclusion disease is a neurodegenerative condition which can be a target for gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Clinical Symptoms ◽  
Repeat Expansion ◽  
Gene Identification ◽  
Therapeutic Assessment ◽  
Causative Gene ◽  
Central Nervous System Disorders ◽  
Number Of Patients ◽  
Mechanism Research ◽  
Or Gene

NIHID (neuronal intranuclear hyaline inclusion disease) is a neurodegenerative condition that is easy to detect but also easy to misdiagnose. Thanks to breakthroughs in MRI detection, the availability of skin biopsied pathology, and, most critically, the finding of the causative gene which can be targeted by gene therapy, the rate of NIID diagnosis before death has grown significantly in recent years. Symptoms linked with central nervous system disorders, autonomic and peripheral neuropathy, and myopathy may be experienced by patients with NIID. Regardless of how far clinical symptoms or gene identification have progressed in NOTCH2NLC gene-related repeat expansion disorders (NRED), it not only adds to our understanding of NIID, but it also adds to the number of challenges we must address. East Asia has seen a substantial number of patients with GGC repeat expansion in NOTCH2NLC. Clinicians should work together to develop a database of NIID clinical and biological samples, as well as perform additional clinical diagnostic, therapeutic assessment, and pathogenic mechanism research.

scholarly journals A Natural History Comparison of SOD1-Mutant Patients with Amyotrophic Lateral Sclerosis between Chinese and German Populations

2021 ◽  
Author(s):  
Lu Tang ◽  
Johannes Dorst ◽  
Lu Chen ◽  
Xiaolu Liu ◽  
Yan Ma ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Large Scale ◽  
Age Of Onset ◽  
Diagnostic Delay ◽  
Chinese Patients ◽  
Common Mutation ◽  
Progression Rate ◽  
Causative Gene ◽  
Sod1 Mutant ◽  
Lateral Sclerosis

Abstract Background: The gene coding the Cu/Zn superoxide dismutase ( SOD1 ) was the first-identified causative gene of amyotrophic lateral sclerosis (ALS), and the second most common genetic cause for ALS worldwide. The promising therapeutic approaches targeting SOD1 mutations are on the road. The purpose of the present study was to compare the mutational and clinical features of Chinese and German patients with ALS carrying mutations in SOD1 gene, which will facilitate the strategy and design of SOD1 -targeted trials.Methods: Demographic and clinical characteristics were collected from two longitudinal cohorts in China and Germany. Chinese and German patients carrying SOD1 mutations were compared with regard to mutational distribution, age of onset, site of onset, body mass index (BMI) at diagnosis, diagnostic delay, progression rate, and survival.Results: A total of 66 Chinese and 84 German patients with 69 distinct SOD1 mutations were identified. The most common mutation in both populations was p.His47Arg. It was found in 8 Chinese and 2 German patients and consistently showed a slow progression of disease in both countries. Across all mutations, Chinese patients showed a younger age of onset (43.9 vs 49.9 years, p=0.002), a higher proportion of young-onset cases (62.5% vs 30.7%, p<0.001) and a lower BMI at diagnosis (22.8 vs 26.0, p<0.001) compared to German patients. Although riluzole intake was less frequent in Chinese patients (28.3% vs 81.3%, p<0.001), no difference in survival between populations was observed (p=0.90). Across both cohorts, female patients had a longer diagnostic delay (15.0 vs 11.0 months, p=0.01) and a prolonged survival (248.0 vs 60.0 months, p=0.005) compared to male patients.Conclusions: Our data demonstrate the distinct mutational and clinical spectrums of SOD1 -mutant patients in Asian and European populations. Clinical phenotypes seem to be primarily influenced by mutation-specific, albeit not excluding ethnicity-specific factors. Further large-scale transethnical studies are needed to clarify determinants and modifiers of SOD1 phenotypes.

Mutation screening and burden analysis of GLT8D1 in Chinese patients with ALS

2020 ◽  
Author(s):  
Bei Cao ◽  
Xiaojing Gu ◽  
Qianqian Wei ◽  
Chunyu Li ◽  
Yongping Chen ◽  
...  
Keyword(s):  
Rare Variants ◽  
Mutation Screening ◽  
Large Cohort ◽  
Chinese Patients ◽  
Causative Gene ◽  
Variant Of Uncertain Significance ◽  
Sporadic Als ◽  
Gene Level ◽  
Exon 4

Abstract Objective Glycosyltransfersase 8 domain containing 1 ( GLT8D1 ) gene was identified to be an amyotrophic lateral sclerosis (ALS) causative gene via pedigree co-segregation and burden analysis. However, validations based on large cohort of ALS among different ethnic population are essential. We aimed to systematically screen all exons of GLT8D1 in a large cohort of Chinese ALS patients, study the genotype-phenotype correlation and explore the role of rare variants of GLT8D1 in ALS.Methods A total of 977 sporadic ALS (sALS) and 47 familial ALS (fALS) cases underwent whole exome sequencing. Rare variants with MAF<0.1% in GLT8D1 were analyzed. Moreover, by using the controls from gnomAD database, rare variants were included in the burden analysis via 5 different algorithms.Results We identified 1 likely pathogenic variant in the exon 4 of GLT8D1 in a fALS case and validated within the pedigree. Moreover, 3 variant of uncertain significance (VUS) in 4 patients among the 977 sALS cases 1 VUS in 1 case among the 47 fALS cases were also identified. Furthermore, in the burden analysis, there were no significant enrichment of rare variants of GLT8D1 in the whole gene level or exon 4 exclusively among Chinese patients with sALS.Conclusion Cosegregation findings in our study further supported the pathogenic role of GLT8D1 in fALS. However, no pathogenic mutation was identified in the sALS patients, and rare variants were not enriched in the whole gene level or exon 4 of GLT8D1 among sALS patients, both of which suggested that the GLT8D1 may not play a role in Chinese patients with sALS.

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