scholarly journals Genetic testing for Spinocerebellar Ataxias (SCA) in Parkinsonism

2013 ◽  
Vol 28 (1) ◽  
pp. 16-23
Author(s):  
Md Siddiqur Rahman ◽  
Yoshitaka Nagai ◽  
H Akiko Popiel ◽  
Muzahed Uddin Ahmed ◽  
Md Jalal Uddin ◽  
...  
Keyword(s):  
Healthy Individual ◽  
Demographic Data ◽  
Venous Blood ◽  
Pcr Amplification ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Clinical Genetics ◽  
Spinocerebellar Ataxias ◽  
Product Size ◽  
Pcr Product

Objective: The study was conducted to find out Spinocerebellar Ataxias (SCA) by genetic analysis from those presenting with parkinsonism in the Neurology department of Mymensingh Medical College.Materials and methods: A sample of about 5ml blood was collected by venipuncture in EDTA tube with informed consent from the patients following institutional ethics committee approval by genetic study from 7 healthy people and 9 patients. The neurological disorder along with a complete physical and/or psychological, as well as family history and demographic data was recorded with a prescribed questionnaire by the neurologists of Mymensingh Medical College. Extraction of genomic DNA from the venous blood using FlexiGene DNA kit (Qiagen, Japan) was performed in Department of Medicine, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh. The extracted DNA was stored and accumulated and then these DNA were sent to Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan for PCR and further analysis. PCR amplification of the CAG repeat was performed for the SCA1, SCA2, SCA3, SCA6 loci using primers SCA1N-F1 and SCA1N-R1, SCA2-F1 and SCA2-R1, MJDF1 and MJDR1, SCA6-F1 and SCA6-R1, respectively.Results: SCA1 PCR of both healthy individual and suspected PD patients DNA is about 250 bp (no. of CAG repeats=36). SCA2 PCR products reveal the DNA products of about 150 bp (no. of CAG repeats=23) except one patient that we suspected and it was sequenced and revealed 175bp (no. of CAG repeats=30). SCA3 PCR product size of both healthy individual and patient DNA is within about 250 (no. of CAG=11) to 300 bp (no. of CAG repeats=28) except one patient which is about 320bp and its CAG repeats is about 34. SCA6 PCR product size of both healthy individual and patient DNA is about 150bp (no. of CAG=16).Conclusion: This is the first time from Bangladesh regarding the range of CAG repeats in patients as well as healthy individual.

scholarly journals Polyglutamine Diseases after Genetic Analysis in Patients Clinically Diagnosed as Parkinson’s Disease in Bangladesh

2016 ◽  
Vol 12 (2) ◽  
pp. 44-49
Author(s):  
Md Siddiqur Rahman ◽  
Md Abu Sayeed Sarker ◽  
Md Fashiur Rahman ◽  
T Toda ◽  
Mohommad Humayun Kabir ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Healthy Individual ◽  
Cag Repeat ◽  
Cag Repeats ◽  
College Hospital ◽  
Product Size ◽  
Medical College ◽  
Pcr Product ◽  
Pcr Products ◽  
Polyq Diseases

Introduction: Polyglutamine (polyQ) diseases are Huntington's Disease (HD), Dentatorubropallidoluysian Atrophy (DRPLA), Spinobulbar Muscle Atrophy (SBMA) and the Spinocerebellar Ataxias (SCA) type 1, 2, 3, 6, 7 and 17. These diseases are characterized by an expansion of the CAG-trinucleotide repeat region in the respective disease-related genes. Objective: To find out Polyglutamine (polyQ) diseases by genetic analysis from those patients presenting with Parkinsonism in the Neurology department of Mymensingh Medical College hospital. Materials and Methods: This study was conducted on 7 healthy people and 9 patients of Neurology Department, Mymensingh Medical College Hospital in 2010. 5ml blood was collected from each individual by venipuncture. The complaints of patients along with physical and/or psychological findings, family history including demographic data were recorded with a questionnaire by the neurologists of Hospital. Informed consents from the patients were taken and ethical clearance sought as well. Extraction of genomic DNA from the venous blood using FlexiGene DNA kit (Qiagen, Japan) was performed in Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh. The extracted DNA was stored, accumulated and were sent to Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan for PCR and further analysis up to amplification. Results: HD PCR products reveal the DNA product of about 110bp (no. of CAG repeats=21) to 150bp (no. of CAG repeats=34) in both healthy individual and patient repeats=36). SCA2 PCR products reveal the DNA products of about 150 bp (no. of CAG repeats=23) except one patient and it was 175bp (no. of CAG repeats=30). SCA3 PCR product size of both healthy individual and patient DNA was within about 250 (no. of CAG=11) to 300 bp (no. of CAG repeats=28) except one patient which was about 320bp and its CAG repeats was about 34. SCA6 PCR product size of both healthy individual and patient DNA was about 150bp (no. of CAG=16). DRPLA PCR product size of healthy individual and patients DNA was about 142 (no. of CAG repeats=19) to 165bp (no. of CAG repeats=27) except one healthy individual DNA which was about 205 bp and its CAG repeat was 40. Conclusion: Genetic analysis and PCR has been an important tool to visualize the root cause of the diseasesthe CAG repeat can facilitate a definitive clue to address Poly Q diseases.This is so far first time study in Bangladesh on the range of CAG repeats in patients as well as healthy individual. Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 44-49

scholarly journals Molecular characteristics of Machado-Joseph disease mutation in 25 newly described Brazilian families

1997 ◽  
Vol 20 (4) ◽  
pp. 717-724 ◽  
Author(s):  
Iscia Lopes-Cendes ◽  
Hélio G.A. Teive ◽  
Francisco Cardoso ◽  
Erika M. Viana ◽  
Maria E. Calcagnotto ◽  
...  
Keyword(s):  
Late Onset ◽  
Age At Onset ◽  
Collaborative Study ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Causative Mutation ◽  
Molecular Characteristics ◽  
Spinocerebellar Ataxias ◽  
Extrapyramidal Signs ◽  
Machado Joseph Disease

Machado-Joseph disease (MJD) is a form of autosomal dominant spinocerebellar ataxia first described in North-American patients originating from the Portuguese islands of the Azores. Clinically this disorder is characterized by late onset progressive ataxia with associated features, such as: ophthalmoplegia, pyramidal and extrapyramidal signs and distal muscular atrophies. The causative mutation is an expansion of a CAG repeat in the coding region of the MJD1 gene. We have identified 25 unrelated families segregating the MJD mutation during a large collaborative study of spinocerebellar ataxias in Brazil. In the present study a total of 62 family members were genotyped for the CAG repeat in the MJD1 gene, as well as 63 non-MJD individuals (126 normal chromosomes), used as normal controls. We observed a wide gap between the size range of the normal and expanded CAG repeats: the normal allele had from 12 to 33 CAGs (mean = 23 CAGs), whereas the expanded alleles ranged from 66 to 78 CAGs (mean = 71.5 CAGs). There were no differences in CAG tract length according to gender of affected individuals or transmitting parent. We observed a significant negative correlation between age at onset of the disease and length of the CAG tract in the expended allele (r = -0.6, P = 0.00006); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2 = 0.4). There was instability of the expanded CAG tract during transmission from parent to offspring, both expansions and contractions were observed; however, there was an overall tendency for expansion, with a mean increase of +2.4 CAGs. The tendency for expansion appeared to the greater in paternal (mean increase of +3.5 CAGs) than in maternal transmissions (mean increase of +1.3 CAGs). Anticipation was observed in all transmissions in which ages at onset for parent and offspring were known; however, anticipation was not always associated with an increase in the expanded CAG repeat length. Our results indicate that the molecular diagnosis of MJD can be confirmed or excluded in all suspected individuals, since alleles of intermediary size were not observed.

scholarly journals The Effect of CAG Repeats within the Non-Pathological Range in the HTT Gene on Cognitive Functions in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1051
Author(s):  
Valentina Bessi ◽  
Salvatore Mazzeo ◽  
Silvia Bagnoli ◽  
Giulia Giacomucci ◽  
Assunta Ingannato ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Ability ◽  
Cognitive Status ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Subjective Cognitive Decline ◽  
Visual Spatial ◽  
Premorbid Intelligence

The Huntingtin gene (HTT) is within a class of genes containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. Individuals with less than 35 repeats are not associated with HD. Increasing evidence has suggested that CAG repeats play a role in modulating brain development and brain function. However, very few studies have investigated the effect of CAG repeats in the non-pathological range on cognitive performances in non-demented individuals. In this study, we aimed to test how CAG repeats’ length influences neuropsychological scores in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We included 75 patients (46 SCD and 29 MCI). All patients underwent an extensive neuropsychological battery and analysis of HTT alleles to quantify the number of CAG repeats. Results: CAG repeat number was positively correlated with scores of tests assessing for executive function, visual–spatial ability, and memory in SCD patients, while in MCI patients, it was inversely correlated with scores of visual–spatial ability and premorbid intelligence. When we performed a multiple regression analysis, we found that these relationships still remained, also when adjusting for possible confounding factors. Interestingly, logarithmic models better described the associations between CAG repeats and neuropsychological scores. CAG repeats in the HTT gene within the non-pathological range influenced neuropsychological performances depending on global cognitive status. The logarithmic model suggested that the positive effect of CAG repeats in SCD patients decreases as the number of repeats grows.

scholarly journals Homozygous spinocerebellar ataxia type 3 in China: a case report

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110213
Author(s):  
Yuchao Chen ◽  
Dan Li ◽  
Minger Wei ◽  
Menglu Zhou ◽  
Linan Zhang ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Clinical Phenotype ◽  
Gene Dosage ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Contraction Pattern ◽  
Spinocerebellar Ataxia Type 3 ◽  
Type 3 ◽  
Stable Transmission

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a heterozygous CAG repeat expansion in the ataxin 3 gene ( ATXN3). However, patients with homozygous SCA3 carrying expanded CAG repeats in both alleles of ATXN3 are extremely rare. Herein, we present a case of a 50-year-old female who had homozygous SCA3 with expansion of 62/62 repeats. Segregation analysis of the patient’s family showed both a contraction pattern of CAG repeat length and stable transmission. The present case demonstrated an earlier onset and more severe clinical phenotype than that seen in heterozygous individuals, suggesting that the gene dosage enhances disease severity.

scholarly journals Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. Methods Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007–2019 in Aragon (Spain). Results 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. Conclusions Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

scholarly journals Suitability of different tissue fixatives for subsequent PCR analysis of Cysticercus ovis

2012 ◽  
Vol 49 (2) ◽  
pp. 67-70 ◽  
Author(s):  
M. Kolesárová ◽  
R. Herich ◽  
M. Levkut ◽  
J. Čurlík ◽  
M. Levkut
Keyword(s):  
Retrospective Studies ◽  
Pcr Amplification ◽  
Pcr Analysis ◽  
Chain Reaction ◽  
Fresh Tissue ◽  
Carnoy’S Solution ◽  
Negative Results ◽  
Pcr Product ◽  
Polymerase Chain ◽  
Cysticercus Ovis

AbstractPCR amplification of specific DNA regions is a powerful tool for retrospective studies, but not all preservation or fixation methods render DNA that is suitable for subsequent amplification. Several factors affect sensitivity of polymerase chain reaction (PCR) amplification. There were reported the effects of commonly used fixation solutions — 10 % neutral buffered formalin, 20 % neutral buffered formalin and Carnoy’s solution and the efficiency of PCR amplification in fresh tissue and paraffin (or wax) embedded samples of Cysticercus ovis. DNA from samples was isolated and PCR product of 1300 bp was amplified. Results indicated that the samples fixed in Carnoy’s solution produced reliable amplification of desired fragments. The samples that were fixed in 10 % and 20 % neutral buffered formalin brought negative results.

scholarly journals The MID1 Protein: A Promising Therapeutic Target in Huntington’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Annika Heinz ◽  
Judith Schilling ◽  
Willeke van Roon-Mom ◽  
Sybille Krauß
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Protein A ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Progressive Movement ◽  
Promising Therapeutic Target ◽  
Promising Therapeutic Approach ◽  
Exon 1 ◽  
Polyglutamine Protein

Huntington’s disease (HD) is caused by an expansion mutation of a CAG repeat in exon 1 of the huntingtin (HTT) gene, that encodes an expanded polyglutamine tract in the HTT protein. HD is characterized by progressive psychiatric and cognitive symptoms associated with a progressive movement disorder. HTT is ubiquitously expressed, but the pathological changes caused by the mutation are most prominent in the central nervous system. Since the mutation was discovered, research has mainly focused on the mutant HTT protein. But what if the polyglutamine protein is not the only cause of the neurotoxicity? Recent studies show that the mutant RNA transcript is also involved in cellular dysfunction. Here we discuss the abnormal interaction of the mutant HTT transcript with a protein complex containing the MID1 protein. MID1 aberrantly binds to CAG repeats and this binding increases with CAG repeat length. Since MID1 is a translation regulator, association of the MID1 complex stimulates translation of mutant HTT mRNA, resulting in an overproduction of polyglutamine protein. Thus, blocking the interaction between MID1 and mutant HTT mRNA is a promising therapeutic approach. Additionally, we show that MID1 expression in the brain of both HD patients and HD mice is aberrantly increased. This finding further supports the concept of blocking the interaction between MID1 and mutant HTT mRNA to counteract mutant HTT translation as a valuable therapeutic strategy. In line, recent studies in which either compounds affecting the assembly of the MID1 complex or molecules targeting HTT RNA, show promising results.

scholarly journals Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

2015 ◽  
Vol 73 (1) ◽  
pp. 18-21 ◽  
Author(s):  
Marcus Vinicius Cristino de Albuquerque ◽  
José Luiz Pedroso ◽  
Pedro Braga Neto ◽  
Orlando Graziani Povoas Barsottini
Keyword(s):  
Spinocerebellar Ataxia ◽  
Early Onset ◽  
Clinical Presentation ◽  
Age Of Onset ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxias ◽  
Phenotype Variability ◽  
Spinocerebellar Ataxia Type 7 ◽  
Early Onset Ataxia

The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

Epidemiology and Pattern of Thromboembolism in Aseer Central Hospital, a Multispecialty Hospital in Aseer Region, Abha in Southern Saudi Arabia

2020 ◽  
Author(s):  
Aziz S
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Demographic Data ◽  
Venous Blood ◽  
Pulmonary Veins ◽  
Lower Limbs ◽  
Central Hospital ◽  
Vein Thrombosis ◽  
Hospitalization Period ◽  
Deep Vein

Background: Venous Thromboembolism (VTE) is a clinical disorder characterized by the pathological occurrence of single or many thrombi developing mainly in the deep veins of the lower limbs and pulmonary veins but also other parts of the venous circulation, albeit less. A frequently occurring venous thrombosis is a deep vein thrombosis (DVT), which is the presence of thrombus in deep veins of the lower extremity. Once this clot fragment is swept off (embolism), it moves along with the venous blood and flows to the pulmonary vessels, where it may result in a clinically significant disorder called pulmonary thromboembolism (PTE). Thrombosis occurring in the superficial veins would only cause discomfort but generally with insignificant consequences. Aim: This study aimed to assess patterns and risk factors of venous thromboembolism (VTE) among patients in the Aseer region. Methodology: A record-based descriptive analysis (retrospective) was used in this study. The clinical study targeted the patients with venous thromboembolism (VTE including PE & DVT) either admitted with the diagnosis or complicated during the hospitalization period in Aseer Central Hospital during the period from January 2010 to June 2019. Data extracted using pre-structured data collection sheet. The extracted data were patients' bio-demographic data, VTE related data, treatment received and relevant complications of treatment, and patient’s follow-up history. Results: The study included total of 207 patients with thromboembolism. The age of patients was between 15 - 100 years old with the average age being 57.3+12.9 years. Approximately 58% of the patients were female. Deep vein thrombosis (DVT) was recorded in 60.4% of the cases and 27.5% of them were diagnosed with pulmonary embolism (PE) while 12.1% had both PE and DVT. Exact of 59.6% of cases with PE had immobilization history for 24 to 72 hours as compared to 31.2% of DVT and 44% of patients with mixed thromboembolism. DM was recorded among 14% of PE cases and 21.6% of DVT. Warfarin with Enoxaparin was the most frequently given treatment in total (23.2%). Heparin followed by Warfarin was the second most common treatment. Conclusions and recommendation: The study revealed that VTE was commonly reported especially DVT and PE among the recorded cases and it was bilateral in a considerable number of cases. Immobilization with chronic disease and morbid obesity was noted as the most significant predictor for VTE.

scholarly journals A Case of Previously Unsuspected Huntington Disease Diagnosed at Autopsy

2017 ◽  
Vol 7 (1) ◽  
pp. 136-144
Author(s):  
Catherine R. Miller ◽  
Nobby C. Mambo ◽  
Jianli Dong ◽  
Gerald A. Campbell
Keyword(s):  
Genetic Testing ◽  
Huntington Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Case Reports ◽  
Neuronal Loss ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Psychiatric Disturbances ◽  
Personality Changes

Huntington disease (HD) is a neurodegenerative disorder with a worldwide prevalence of four to ten per 100 000. It is characterized by choreiform movements, behavioral/psychiatric disturbances, and eventual cognitive decline. Symptoms usually present between 30 and 50 years of age and the diagnosis is based on the combination of clinical symptoms, family history, and genetic testing. A variation of HD, juvenile Huntington disease (JHD), presents earlier, with more severe symptoms and with a worse prognosis. Symptoms are different in JHD, with personality changes and learning difficulties being the predominant presenting features. Seizures are common in JHD, and chorea is uncommon; movement disorders at presentation of JHD are predominantly nonchoreiform. The inheritance pattern for both HD and JHD is autosomal dominant and the disease is caused by an elongation of the CAG repeat in the huntingtin gene. There are many published case reports of Huntington disease that were confirmed at autopsy, but to our knowledge, there are no reports in the literature where the diagnosis of Huntington disease was first made at autopsy. We present a case of a 28-year-old African-American male who was in a state of neglect due to a lifetime of abuse, cognitive difficulties, and seizures, whose cause of death was pneumonia. The gross autopsy findings included bilateral caudate nucleus atrophy and lateral ventricular dilation. Microscopically, severe bilateral neuronal loss and gliosis of the caudate and putamen nuclei were seen. Genetic testing for the number of CAG repeats confirmed the diagnosis and was consistent with JHD.

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