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Objective:To report the clinical manifestation and genetic characteristics of a case of de novo Huntington′s disease due to paternal intermediate alleles. Methods:Clinical data and imaging features of a middle-aged female, who complained of unstable walking without positive family history and was admitted to Xuanwu Hospital, Capital Medical University on September 20, 2022, were retrospectively analyzed. The serum samples of the patient and her parents were used to screen HTT gene dynamic mutation in accordance with the principle of informed consent and voluntary. And the relevant literatures were reviewed. Results:This is a 38-year-old female with progressive course, who presented as ataxia, involuntary movement at the end of extremities, dystonia, and cognitive impairment. Imaging results showed atrophy of bilateral caudate nuclei, as well as decreased glucose metabolism of bilateral caudate nuclei, putamen and partial cortex. Genetic testing showed the abnormal expansion of polymorphic trinucleotide (CAG) repeats in HTT gene and confirmed the diagnosis of Huntington′s disease. The CAG repeat length of the patient was 17/47 (pathopoiesis), of the father was 17/35 (intermediate alleles), and of the mother was 17/17 (normal). Conclusions:Paternal intermediate alleles may cause the first case of Huntington′s disease in a family. Importantly, HTT gene screening should be performed for the patient and parents when the diagnosis of Huntington′s disease is clinically possible despite negative family history, to prevent the misdiagnosis.
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Introduction: Huntington's disease (HD) is a neurodegenerative disorder caused by CAG expansion repeats in the HTT gene. Usually, the symptoms start to manifest in mid-adulthood. In about 5% of cases, however, the signs begin before the age of 20 years. These cases are known as juvenile HD (JHD). Objective: here we report a case series of JHD from Amazonas, a state where data are scarce due to the restricted access to specialized medical assistance for diagnosis and care. Case series: the patients were attended by neurologists specialized in movement disorders at Manaus. Two cases manifested the disease in childhood (6 and 7 years old) and two cases, in adolescence (12 and 16 years old). All cases showed dystonia and parkinsonism as predominant motor disorders. Moreover, signs of cognitive decline, depression, and psychosis were observed in all patients. Conversely, cerebellar signs, gait disturbances, seizures, and some psychiatric symptoms were variable among the cases. Expansion size varied from 66 to 84 to CAG repeats and the difference in age at onset between parent and child varied from 23 to 43 years. Conclusion: to our knowledge, these are the first clinical reports of JHD in northern Brazil. These cases illustrate the variability in clinical phenotypes and genetic features of JHD cases. Furthermore, they can contribute to the awareness of HD here, both by professionals and the public in general.
Introdução: a doença de Huntington (DH) é um distúrbio neurodegenerativo causado pela expansão de repetições CAG no gene HTT. Geralmente, os sintomas começam a se manifestar na vida adulta tardia. Em cerca de 5% dos casos, no entanto, os sinais começam antes da idade de 20 anos. Esses casos são conhecidos como DH juvenil (DHJ). Objetivo: neste estudo, nós reportamos uma série de casos de DHJ do Amazonas, um estado onde os dados ainda são escassos devido ao acesso restrito à assistência médica especializada para o diagnóstico e cuidado. Série de casos: os pacientes foram atendidos por neurologistas especializados em transtornos do movimento em Manaus. Dois casos manifestaram a doença na infância (6 e 7 anos) e dois casos, na adolescência (12 e 16 anos). Todos os casos apresentaram distonia e parkinsonismo como sintomas motores predominantes. Sinais de declínio cognitivo, depressão e psicose também foram observados em todos os pacientes. Por outro lado, sinais cerebelares, distúrbios da marcha, convulsões e alguns sintomas psiquiátricos foram variáveis entre os casos. O tamanho da expansão CAG variou de 66 a 84 repetições e a diferença na idade de início dos sintomas entre pais e filhos variou de 23 a 43 anos. Conclusão: ao nosso conhecimento, estes são os primeiros relatos clínicos da DHJ na região Norte. Esses casos ilustram a variabilidade nos fenótipos clínicos e nas características genéticas dos casos de DHJ. Além disso, eles podem contribuir para a conscientização da DH na região, tanto pelos profissionais quanto pelo público geral.
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Humans , Male , Female , Child , Adolescent , Adult , Huntington Disease , Trinucleotide Repeat Expansion , Anticipation, Genetic , Heredodegenerative Disorders, Nervous System , Biological Variation, PopulationABSTRACT
Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.
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Objective:To investigate the clinical and genetic characteristics of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with replication factor C subunit 1 (RFC1) gene mutation to improve the understanding of this disease.Methods:A case of CANVAS diagnosed in the Peking University Third Hospital in January 2021 was reported. Detailed genetic analyses of ataxia were performed with DNA extracted from the peripheral blood of the patient. Studies including pathogenic variants of RFC1 gene causing CANVAS were reviewed and the clinical and genetic characteristics of the disease were summarized.Results:The patient was a 51-year-old female with the prominent manifestation of progressive walking instability. And the clinical data met the diagnostic criteria of CANVAS. The genetic tests excluded other hereditary ataxia mutations and identified the biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in RFC1 gene. A total of 14 studies on CANVAS with RFC1 gene mutation were reviewed. The overall mutation rate of RFC1 gene in CANVAS was 68%-100%, and it varied in sporadic and familial CANVAS. And the mutation had ethnic differences.Conclusions:Among adult patients with late-onset ataxia, the combination of brain magnetic resonance imaging, electrophysiology tests and vestibular function examination is beneficial to the identification of CANVAS. And the genetic test of RFC1 gene has significant value in the diagnosis of this disease. This patient with CANVAS expands the disease spectrum of ataxia in China, and confirms that RFC1 gene mutation is of great significance in the screening of ataxia disorders in the Chinese population.
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Nucleotide repeat expansion is one of the common causes for neurodegenerative disorders. Polyglycine diseases are a newly defined neuro- and muscle- degenerative disease spectrum characterized by CGG trinucleotide repeat expansions, generation and aggregation of aberrant polyglycine protein, and formation of intranuclear inclusions. To date, the aggregation of pathogenic polyglycine protein has been proved in fragile X-associated tremor/ataxia syndrome and neuronal intranuclear inclusion disease. In recent years, the case load of these diseases grows rapidly with the increasing awareness and developing genetic testing technologies. This article aims to systematically review the recent progress in polyglycine diseases, and probe into their pathogenic mechanisms as well as clinical concerns.
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Objective To investigate the features of molecular genetics of 4 Huntington's disease (HD) pedigrees in Xinjiang.Methods Collected for this study were the data of the HD patients who had been admitted by Department of Neurology,The First Affiliated Hospital to Xinjiang Medical University from August 2010 to June 2017 and the genetic data of their 4 HD pedigrees of altogether 15 members.Their mutations of HTT gene amplification of CAG trinucleotide were detected with the polymerase chain reaction and capillary electrophoresis.Their test results and genetic characteristics were analyzed respectively.Results The 4 pedigrees of HD included 3 Han families and one Hui family.The 4 HD patients confirrned were one male and 3 females;their onset age ranged from 21 to 47 years old;their CAG copy number ranged from 42 to 62 times.The 3 presymptomatic patients were 2 males and one female,aged from 27 to 31 years old;their CAG copy number ranged from 44 to 48 times.The CAG copy number ranged from 16 to 20 times in the normal family members of the 4 HD pedigrees.Conclusions The CAG copy number may be increased and anticipation may exist in the HD patients by paternal inheritance.
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Introducción: La distrofia miotónica es una enfermedad poco frecuente de origen genético. Se produce por aumento de repeticiones de la tripleta CTG en el gen DMPK (locus 19q13.32), o por aumento de repeticiones de CCTG en el gen ZNF9 (locus3q21.3). Su fenotipo es variable y sus principales características son la debilidad muscular progresiva y la miotonía. El objetivo de esta publicación es reportar un caso colombiano de distrofia miotónica tipo 1 con diagnóstico molecular y contribuir a la construcción de datos epidemiológicos locales sobre esta patología. Además, aportar información a médicos generales, pediatras, internistas, fisiatras, neurólogos, y en general al personal de salud que puede tener contacto con pacientes con debilidad muscular progresiva, escenario en el cual la distrofia miotónica es una posibilidad diagnóstica a considerar. Descripción del caso: Hombre de 37 años, con historia de pobre succión neonatal, retraso en los hitos del desarrollo, discapacidad intelectual y, en la adolescencia, aparición de debilidad progresiva generalizada, miotonía y disfagia. El Southernblot y PCR del gen DMPK mostraron un alelo expandido en un rango entre 1100 a 1700 repeticiones del triplete CGT y un alelo normal, confirmando el diagnóstico de distrofia miotónicatipo 1. Conclusión: El paciente aquí reportado presentó fenotipo sugestivo de DM1; el diagnóstico fue confirmado con la prueba molecular. Con el resultado fue posible realizar una consejería genética adecuada y brindar información sobre la enfermedad.
Introduction: Myotonic dystrophy (MD) is a rare genetic disease. It is produced by an increased repetition of the CTG triplet in the DMPK gene (locus 19q13.32), or by increasing repetitions of CCTG in the ZNF9 gene (locus 3q21.3). Its phenotype is variable, and its key features are progressive muscle weakness and myotonia. The aim of this publication is to report a Colombian case of myotonic dystrophy type 1 with molecular diagnosis and to contribute to the construction of local epidemiological data on this pathology. Also, to provide information to general practitioners, pediatricians, internists, physiatrists, neurologists, and health personnel who may have contact with patients with progressive muscle weakness, scenario in which myotonic dystrophy is a diagnostic possibility to be considered. Case description: Thirty-seven year old male with a history of poor neonatal suction, delay in developmental milestones, intellectual disability and, in adolescence, the onset of progressive generalized weakness, myotonia and dysphagia. Southern blot and PCR of DMPK gene showed one expanded allele in a range between 1100-1700 repetitions of the CGT triplet and one normal allele, confirming the diagnosis of myotonic dystrophy type 1. Conclusion: The patient reported here presented a phenotype suggestive of myotonic dystrophy type 1; the diagnosis was confirmed by molecular testing. This result made it possible to offer a proper genetic counseling and provide information about the disease.
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PURPOSE: We examined the prevalence and CGG/AGG repeat structure of expanded alleles of the FMR1 gene in preconceptional and pregnant Korean women. MATERIALS AND METHODS: The CGG repeats in the FMR1 genes of 1,408 women were analyzed by polymerase chain reaction and Southern blot analysis. To estimate the prevalence of expansion alleles, the individuals were divided into low risk and high risk group. RESULTS: Within this population, 98.4% had normal alleles and 1.6% had abnormal alleles including intermediate (0.6%), premutation (0.5%), full mutation (0.1%), and hemizygous (0.4%) alleles. There were 2 premutation alleles (1:666, 95% confidence interval [CI] 1:250-1,776) in the low risk group and 5 premutation alleles (1:15, 95% 1:6-36) in the high risk group. There were 8 intermediate alleles (1:167, 95% CI 1:130-213) in the low risk group and 1 intermediate alleles (1:76, 95% CI 1:11-533) in the high group. Six of the 7 premutation alleles did not contain AGG interruptions within the repeats and 1 had a single AGG interruption. Four of the 9 intermediate alleles contained 2-3 AGG, 4 had a single AGG, and 1 had no AGG interruptions. CONCLUSION: Our study demonstrates the prevalence and CGG/AGG structure of expansion alleles in Korean women. The identified premutation prevalence is higher than that of other Asian populations and lower than that of Caucasian populations. Although our study is limited by size and population bias, our findings could prove useful for genetic counseling of preconceptional or pregnant women.
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Female , Humans , Alleles , Asian People , Bias , Blotting, Southern , Carrier State , Fragile X Syndrome , Gene Frequency , Genetic Counseling , Mass Screening , Polymerase Chain Reaction , Pregnant Women , Prevalence , Trinucleotide Repeat ExpansionABSTRACT
Objective To analyze the clinical features of 35 cases of Kennedy's disease and the correlation be?tween clinical features and CAG repeat size to strengthen the understanding of KD and to avoid misdiagnosis and delayed diagnosis.Methods Clinical data, including clinical signs and symptoms ,serum lipid, serum sex hormone level, electro?myography, the number of CAGs and (amyotrophic lateral sclerosis muscular atrophy,ALS) rating scale were collected from 35 patients genetically diagnosed of Kennedy disease and proceed system analysis. Results Patients with KD were adult onset with the average age of (40.77 ± 8.57) years and the average confirmed course were (8.32 ± 4.17) years. Forty-two point nine percent of the patients had family history. Clinical features included medulla oblongata and spinal muscular atrophy and weakness, limbs tremor, perioral muscles twitch and endocrine function and metabolic disorders in some cases. Creatine kinase, triglyceride, low density lipoprotein, follicle estrogen and prolactin were significantly in?creased compared to healthy adults (P:0.000,0.018,0.000,0.000,0.003). The number of CAG repeat was negatively correlated with the onset age (r=-0.549, P=0.001) but not associated with the illness severity (ALS rating scale) (r=0.001, P=0.998). ALS score was negatively correlated with course of disease(r=-0.540, P=0.001).Conclusions Chinese KD pa? tients share similar clinical phenotypes with those of other races but exhibit slightly different clinical characteristics. The length of the CAG repeat influences age at onset but not the severity of disease. Severity of disease is related to the course of disease.
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Objective To study the clinical characteristics and gene mutation of hereditary spinocerebellar ataxia type 7 (SCA7). Methods The regions of SCA 7 gene containing CAG repeat were amplified by means of PCR and agarose gelelectrophoresis (AGE) technique in 26 patients and 37 normal family members from 5 families with autosomal dominant SCA. The abnormal allele fragments were sequenced by DNA sequencing machine. The correlation between clinical manifestations and CAG repeat size in SCA 7 gene product was analyzed. Results The patients carried 44-50 repeated CAG in the SCA7 allele of 2 SCA 7 gene families with main clinical manifestations as ataxia, hypopsia and retinal pigmental degeneration. About 10-30 repeated CAGs in the SCA7 allele were seen in other healthy members. Conclusion Expanded triplet repeats in SCA 7 gene contributes to the pathologic phenotype,and molecular genetic analysis is effective in the diagnosis and differentiation of SCA 7 gene.
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Introdução: A presença de sequências repetidas de DNA já foi identificada como marcadoras de certas doenças neuropsiquiátricas. O gene FMR1 possui sequência rica em repetições CGG, sujeito a expansão quando transmitido por via materna. Alelos pré-mutados (55
Introduction: The presence of repeated sequences was already identified as markers of neuropsychiatric diseases. The FMR1 gene shelters a CGGrich sequence which is vulnerable to expansion when transmitted through maternal lineage. Premutated alleles (55
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Humans , Aged , Chromosomes, Human, X , Fragile X Mental Retardation Protein , Fragile X Syndrome , Genetic Diseases, X-Linked , Trinucleotide Repeat ExpansionABSTRACT
Myotonic dystrophy type 1 (DM1), which is a dominantly inherited neurodegenerative disorder, results from a CTG trinucleotide repeat expansion in the 3'-untranslated region (3'-UTR) of the myotonic dystrophy protein kinase (DMPK) gene. Retention of mutant DMPK (mDMPK) transcripts in the nuclei of affected cells has been known to be the main cause of pathogenesis of the disease. Thus, reducing the RNA toxicity through elimination of the mutant RNA has been suggested as one therapeutic strategy against DM1. In this study, we suggested RNA replacement with a trans -splicing ribozyme as an alternate genetic therapeutic approach for amelioration of DM1. To this end, we identified the regions of mDMPK 3'-UTR RNA that were accessible to ribozymes by using an RNA mapping strategy based on a trans - splicing ribozyme library. We found that particularly accessible sites were present not only upstream but also downstream of the expanded repeat sequence. Repair or replacement of the mDMPK transcript with the specific ribozyme will be useful for DM1 treatment through reduction of toxic mutant transcripts and simultaneously restore wild-type DMPK or release nucleus-entrapped mDMPK transcripts to the cytoplasm.
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Cytoplasm , Myotonic Dystrophy , Neurodegenerative Diseases , Protein Kinases , Protein Serine-Threonine Kinases , Retention, Psychology , RNA , RNA, Catalytic , Trinucleotide Repeat ExpansionABSTRACT
BACKGROUND: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant muscular dystrophy caused by expansion of cytosine-thymine-guanine (CTG) trinucleotide repeats in the myotonic dystrophy protein kinase (DMPK) gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. The aim of this study was to characterize the molecular and clinical spectra of DM1 in Koreans. METHODS: The CTG repeats of 283 Korean individuals were tested by PCR fragment analysis and Southern blot. The following characteristics were assessed retrospectively: spectrum of CTG expansions, clinical findings, genotype-phenotype correlation, anticipation, and genetic instability. RESULTS: One-hundred twenty-four patients were confirmed as DM1 by molecular tests, and the CTG expansions ranged from 50 to 2,770 repeats (median 480 repeats). The most frequent clinical features were myotonia, muscular weakness, and family history. Patients with muscular weakness or dysfunction of the central nervous system harbored larger CTG expansions than those without each symptom (P<0.05). The age of onset was inversely correlated with the size of the CTG expansion (gamma=-0.422, P<0.001). The instability of CTG expansion representing as the maximum difference between sibships was observed from 50 to 700 repeats in nine families. Clinical anticipation and the increase in CTG repeat were significantly higher in maternally transmitted alleles (P=0.002). CONCLUSIONS: Molecular genetic tests are not only essential for diagnosis, but also helpful for suggesting the spectrum and relationship between genotype and phenotype in Korean DM1 patients.
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Female , Humans , Male , Blotting, Southern , Data Interpretation, Statistical , Genotype , Korea , Myotonic Dystrophy/diagnosis , Pedigree , Phenotype , Polymerase Chain Reaction , Protein Serine-Threonine Kinases/genetics , Retrospective Studies , Trinucleotide Repeat Expansion/geneticsABSTRACT
I previously reported the PCR-based Spinal and bulbar muscular atrophy (SBMA) region polymorphisms in the three northeast Asian populations (Chinese, Koreans, Japanese) and Caucasians. Here I update this analysis by including the data of the allele distribution in 378 unrelated individuals from four populations in Asia. In this study I investigated PCR-based CAG repeat polymorphism on the SBMA locus among four Asian populations (Mongolian, Evenki, Orochon, Negrito) and performed the statistical analysis on the eight populations including the previously analyzed data. Both statistical analyses of one-way ANOVA (F=3.284, P=0.002) and Kruskal-Wallis test (chi-square=21.542, DF=7, P=0.003) showed remarkable differences in CAG allele distributions among the populations. Post-hoc test showed that the difference between Negritos and Caucasians was especially significant (Scheffe: P=0.042; Bonferroni: P=0.004). Also a significant differences among Northeast Asians, Caucasians and Negritos (Southeast Asian) were detected by these two tests (ANOVA; F=8.132, P.0.000, Kruskal-Wallis; chi-square=16.614, DF=2, P.0.000). Post-hoc test showed that the differences between Negritos and Caucasias was also especially significant (Scheffe: P=0.001; Bonferroni: P=0.000) among these three groups. These data present that the CAG repeat polymorphism of SBMA gene has a useful information for studies of human population genetics.
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Humans , Alleles , Asia , Asian People , Genetics, Population , Muscular Disorders, Atrophic , Trinucleotide RepeatsABSTRACT
Background: Fragile X syndrome is the most common cause of inherited X-linked mental retardation. It is due to a mutation in a gene on X chromosome leading to hyper-expansion of a trinucleotide repeat sequence. The two most common Fragile sites with clinical significance are FRAXA at Xq27.3 comprising CGG repeat and a more distal FRAXE associated with amplification of a GCC repeat, located at Xq28. The frequency of occurrence of Fragile X syndrome is estimated to be 1/4000 male births. Screening of referrals for the mutations associated with the Fragile X syndrome constitutes a significant workload in many genetic laboratories. Aims: The aim of the present study was to establish the use of PCR based simple and rapid method of initial screening of samples, so that only a minority of samples tested positive with the above methods need to be screened by Southern blotting which is more time consuming and involves use of radioactive material. materials and Methods: Study includes 294 patients with mental retardation. DNA extracted from blood was used for simultaneous amplification of the triplet repeat sequences at the FRAXA and FRAXE loci. Secondly samples from females were analyzed for heterozygosity of normal FRAXA allele. For confirmation of the presence of an expanded FRAXA allele in all the male positive cases, Southern blot hybridization was carried out. PCR based assay was done to detect methylation of the CpG island upstream of the FMR-1 gene. Results: Out of the 294 cases 23 (7.8%) were found to be having full mutation (FM) for FRAXA (21 males, 1 female & 1 male with mosaic FM/PM) and 13 females as having premutation (PM). All these 36 cases were confirmed by Southern blotting using appropriate probes. Among the females the heterozygosity for FRAXA allele was found to be 46%. Conclusion: Non-radioactive PCR methods are efficient and rapid test for intial screening of samples for the presence of FRAXA and FRAXE mutations. Since a large majority of referrals do not have Fragile X, this economical and reliable method reduces the number of samples needing Southern blotting.
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Dentatorubropallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder usually inherited in an autosomal dominant pattern. DRPLA has been shown to be associated with expansion of an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat in a gene on chromosome 12p. We evaluated a family with DRPLA that affected three members; A 35-year-old female presented with seven year history of gait ataxia, dysarthria and mild cognitive impairment. The MRI of the brain revealed diffuse cerebellar atrophy with an incidental lipoma in the midbrain. Her 30-year-old brother presented with progressive cerebellar ataxia that developed at the age of 20. Her grandmother and mother were reported to have developed ataxia during the late period of their life, and died at the age of 60 and 55, respectively. The demonstration of an expanded CAG repeat in the gene for DRPLA was used to confirm the diagnosis.
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Adult , Female , Humans , Ataxia , Atrophy , Brain , Cerebellar Ataxia , Diagnosis , Dysarthria , Gait Ataxia , Genes, vif , Lipoma , Magnetic Resonance Imaging , Mesencephalon , Cognitive Dysfunction , Mothers , Neurodegenerative Diseases , Siblings , Trinucleotide RepeatsABSTRACT
BACKGROUND: Trinucleotide repeat (TNR) expanded disorders represent a novel class of human mutations, which are characterized by abnormal elongation of the triplet repeat sequence in the human genome and is caused by heritable DNA instability. The aim of this study is to determine the relative frequency, distribution of alleles, and the clinical manifestation of TNR expanded disorders in Korean patients with progressive ataxia. METHODS: A total of 76 clinical specimens that were suspicous of hereditary cerebellar ataxia were submitted from January 1999 to August 2001 and tested for TNR expanded disorders by PCR analysis. RESULTS: Spinocerebellar ataxia (SCA) type 1 was the most common hereditary ataxia (5.3%), while SCA2, SCA3, SCA6, SCA7, and dentatorubral and pallidoluysian atrophy (DRPLA) represented 2.6%, 3.9%, 2.6%, 2.6%, and 1.3% of progressive ataxia patients, respectively. This result is different from previous reports concerning Caucasian, Chinese and Koreans. CONCLUSIONS: This study may provide the basis for the study of TNR expanded disorders in Korean patients. To elucidate the prevalence and frequencies of mutation types in Koreans, a large scale study should be performed.
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Humans , Alleles , Asian People , Ataxia , Atrophy , Cerebellar Ataxia , DNA , Genome, Human , Polymerase Chain Reaction , Prevalence , Spinocerebellar Ataxias , Spinocerebellar Degenerations , Trinucleotide Repeat Expansion , Trinucleotide RepeatsABSTRACT
OBJECTS:We investigated a possible association between the polymorphic trinucleotide repeat(TNR) expansion in neuronal potassium channel gene KCNN3 and schizophrenia. METHODS: CAG/CTG repeat distribution in KCNN3, CTG18.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection(RED) was measured in Korean patients with schizophrenia(n=245) and ethnically matched healthy controls(n=116). RESULTS: Longer alleles in the KCNN3 gene were over-represented in patients. The frequency of alleles with CAG repeats longer than 19 copy in the KCNN3 gene was higher in the patients with schizophrenia as compared to controls(73.3% vs. 65.1%;p=0.029, Fisher's exact test). And this difference was more prominent in schizophrenic patients with familial background(p=0.03, Fisher's exact test). We found no difference in the frequency of longer alleles between negative and positive subtypes of schizophrenia. Ligation product size in RED and alleles with CAG repeat number in the CTG18.1 gene was not increased in the patients. The copy number of ligation product in RED was highly correlated with CAG/CTG copies of ERDA1 in the patient group(r=0.45, p<0.001) as well as in the control group(r=0.44, p<0.001). However, CAG repeat length in the KCNN3 gene was not correlated with ERDA1 score. CONCLUSIONS: Our results support the hypothesis that the longer allele of KCNN3 may be considered as a candidate gene for schizophrenia, especially in the case with familial background. And the RED assay results was affected by the CAG copy number of ERDA1.
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Humans , Alleles , Ligation , Neurons , Potassium Channels , SchizophreniaABSTRACT
The dentatorubropallidoluysian atrophy (DRPLA) is a neurodegenerative disorder with expansion of an unstable CAG trinucleotide repeat in a gene on chromosome 12 and a rare cause of progressive myoclonus epilepsy (PME). A 34-year-old female showed progressive myoclonus, choreoathetosis, generalized tonicclonic seizure, dementia and ataxia. Her uncle died during convulsion at the age of 19. Brain MRI revealed cerebral, cerebellar and brainstem atrophy accompanied by dilatation of the fourth ventricle. The demonstration of expanded CAG repeat (67/11) in the gene for DRPLA was used to confirm the diagnosis. (J Korean Neurol Assoc 19(2):173~175, 2001)