Hsu S.C.,University of California at Los Angeles |
Sears R.L.,University of California at Los Angeles |
Lemos R.R.,University of Santiago de Compostela |
Lemos R.R.,Federal University of Pernambuco |
And 58 more authors.
Neurogenetics | Year: 2013
Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. © 2013 Springer-Verlag Berlin Heidelberg.
Legati A.,University of California at Los Angeles |
Legati A.,Kaiser Permanente |
Giovannini D.,French National Center for Scientific Research |
Giovannini D.,Montpellier University |
And 61 more authors.
Nature Genetics | Year: 2015
Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC. © 2015 Nature America, Inc. All rights reserved.
Rattanawong P.,Mahidol University |
Vutthikraivit W.,Buriram Hospital |
Charoensri A.,Buriram Hospital |
Jongraksak T.,Buriram Hospital |
And 5 more authors.
Annals of Noninvasive Electrocardiology | Year: 2016
Background Brugada syndrome (BrS) is defined as presenting of type-1 Brugada pattern (BrP). BrS can also be induced by fever. This study demonstrated a highest prevalence of fever-induced BrS ever reported. Method During May 2014, febrile (oral temperature ≥ 38 °C) and nonfebrile patients underwent standard and high leads (V1 and V2 at 2nd intercostal space) electrocardiogram. Risk factor and cardiac symptoms were recorded. Patients with a persistent of type-1 BrP after fever had subsided were excluded. The prevalence of BrS, type-2 BrP and early repolarization pattern (ERP) were demonstrated. Results A total of 401 patients, 152 febrile, and 249 nonfebrile, were evaluated. BrS was identified in six febrile patients (five males and one female) and two males in nonfebrile patients. The study demonstrated higher prevalence of BrS in febrile group compared to nonfebrile group (4.0% vs 0.8%, respectively, P = 0.037). Among fever-induced BrS patients, three patients (50.0%) experienced cardiac symptoms before and at the time of presentation and two patients (33.3%) had history of first-degree relative sudden death. No ventricular arrhythmia was observed. All of type-1 BrP disappeared after fever had subsided. We found no difference in prevalence of type-2 BrP in febrile and nonfebrile group (2.0% vs 2.8%, respectively, P > 0.05) as well as ERP (3.3% vs 6.4%, respectively, P > 0.05). Conclusions Our study showed a highest prevalence of fever induced BrS ever reported. A larger study of prevalence, risk stratification, genetic test and management of fever-induced BrS should be done, especially in an endemic area. © 2015, Wiley Periodicals, Inc.
Choubtum L.,Mahidol University |
Witoonpanich P.,Mahidol University |
Hanchaiphiboolkul S.,Prasat Neurological Institute |
Bhidayasiri R.,Chulalongkorn University |
And 5 more authors.
BMC Neurology | Year: 2015
Background: About 50% of Thai patients with adult-onset spinocerebellar ataxia (SCA) was Machado-Joseph disease (MJD), SCA1, SCA2 and SCA6. The author investigated further on less common SCAs in the patients without any known mutations. Methods: DNA samples of 82 index patients who were genetically excluded MJD, SCA1, SCA2, SCA6, SCA7 and dentatorubro-pallidoluysian atrophy (DRPLA) were examined. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 genes were comprehensively performed. Normal range of trinucleotide repeat expansion sizes of TATA-box-binding protein gene (TBP) were also determined in 374 control subjects. Results: Eight patients carried ≥42 CAG/CAA repeat allele in the TBP consistent with SCA17. The pathological repeat alleles ranged from 42 to 57 repeats. All patients had significant degree of cognitive dysfunction. Other non-ataxic phenotypes comprised of parkinsonism, chorea, dystonia and myoclonus. A sporadic patient carried a heterozygous 41-repeat allele developed chronic progressive cerebellar degeneration commenced at the age of 28years. Whilst, 2% of the control subjects (8/374) carried the 41-repeat allele. Five of the carriers were re-examined, and revealed that four of them had parkinsonism and/or cognitive impairment without cerebellar signs. Analysis of other types of SCAs was all negative. Conclusions: This is the first study of SCA8, SCA10, SCA12, SCA17 and SCA19 in Thais. SCA17 appears to be an important cause of ataxia in Thailand. Although, the pathological cut-off point of the TBP repeat allele remains unclear, the finding suggests that the 41-repeat may be a pathological allele resulting late-onset or mild phenotype. Apart from ataxia, cognitive impairment and parkinsonism may be clinical presentations in these carriers. © 2015 Choubtum et al.
Boonkongchuen P.,Mahidol University |
Pongpakdee S.,Bhumibol Adulyadej Hospital |
Jindahra P.,Mahidol University |
Papsing C.,Mahidol University |
And 10 more authors.
BMC Neurology | Year: 2014
Background: Non-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes.Methods: 131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat.Results: Mean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease.Conclusions: We described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs. © 2014 Boonkongchuen et al.; licensee BioMed Central Ltd.
PubMed | Chulalongkorn University, Mahidol University, Buriram Hospital, Bhumibol Adulyadej Hospital and Prasat Neurological Institute
Type: | Journal: BMC neurology | Year: 2015
About 50% of Thai patients with adult-onset spinocerebellar ataxia (SCA) was Machado-Joseph disease (MJD), SCA1, SCA2 and SCA6. The author investigated further on less common SCAs in the patients without any known mutations.DNA samples of 82 index patients who were genetically excluded MJD, SCA1, SCA2, SCA6, SCA7 and dentatorubro-pallidoluysian atrophy (DRPLA) were examined. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 genes were comprehensively performed. Normal range of trinucleotide repeat expansion sizes of TATA-box-binding protein gene (TBP) were also determined in 374 control subjects.Eight patients carried 42 CAG/CAA repeat allele in the TBP consistent with SCA17. The pathological repeat alleles ranged from 42 to 57 repeats. All patients had significant degree of cognitive dysfunction. Other non-ataxic phenotypes comprised of parkinsonism, chorea, dystonia and myoclonus. A sporadic patient carried a heterozygous 41-repeat allele developed chronic progressive cerebellar degeneration commenced at the age of 28years. Whilst, 2% of the control subjects (8/374) carried the 41-repeat allele. Five of the carriers were re-examined, and revealed that four of them had parkinsonism and/or cognitive impairment without cerebellar signs. Analysis of other types of SCAs was all negative.This is the first study of SCA8, SCA10, SCA12, SCA17 and SCA19 in Thais. SCA17 appears to be an important cause of ataxia in Thailand. Although, the pathological cut-off point of the TBP repeat allele remains unclear, the finding suggests that the 41-repeat may be a pathological allele resulting late-onset or mild phenotype. Apart from ataxia, cognitive impairment and parkinsonism may be clinical presentations in these carriers.
Luangkwan S.,Buriram Hospital |
Vetchapanpasat S.,Buriram Hospital |
Panditpanitcha P.,Buriram Hospital |
Yimsabai R.,Suranaree University of Technology |
And 3 more authors.
Journal of the Medical Association of Thailand | Year: 2015
Background: Babies with low birth weight, small for gestational age (SGA) and large for gestational age (LGA) are at increased risk of many perinatal complications. Objective: To evaluate the risks factors associated with SGA and LGA births at Buriram Hospital. Material and Method: Pregnant women who were admitted to the labor room at Buriram hospital were selected, alternate cases in the daytime between October 2012 and January 2013. Pre-pregnancy BMI and gestational weight gain were categorized based on Institute of Medicine BMI groups. The predicted risk of either SGA or LGA births were estimated using generalized linear modeling and multivariate regression. Results: Data were collected on 197 pregnant women including pregnancy characteristics, antenatal care, labor characteristics, maternal complications and neonatal health. The average maternal age was 25.74±6.47 years old. The results showed that the factors of weight gain during pregnancy
Pheerawong P.,Buriram Hospital |
Songmuang S.B.,Chulalongkorn University |
Lertsuwunseri V.,Chulalongkorn University |
Satitthummanid S.,Chulalongkorn University |
Srimahachota S.,Chulalongkorn University
Journal of the Medical Association of Thailand | Year: 2015
Background: In patient with non-valvular atrial fibrillation (AF), over 90% of thrombus accumulation originates in the left atrial appendage (LAA). Warfarin significantly reduces risk of stroke. However, long-term anticoagulant therapy is associated with a significant risk of major bleeding, particularly in elderly. Transcatheter occlusion of left atrial appendage with Watchman device has proved to be non-inferior to warfarin in preventing stroke in non-valvular AF patients. No previous report of transcatheter occlusion of LAA was found in Thailand. Objective: To evaluate short-term results of left atrial appendage closure with the Watchman® device in patient with non-valvular AF performed at King Chulalongkorn Memorial Hospital (KCMH). Material and Method: Between November 2012 and December 2014, 12 consecutives patients underwent percutaneous transcatheter left atrial appendage closure. Data included patient’s characteristics, embolic risk factors, bleeding risk score, procedural finding, complications, in-hospital outcomes, and antithrombotic management were retrospectively reviewed. Results: Percutaneous LAA occlusion was successfully performed in all 12 patients. The mean age was 71.2±8.1 years. The history of previous bleeding was seen in four patients (33%). All patients had good left ventricular systolic function. The mean CHADS2score was 3.2±1.3, the mean CHA2DS2-VASc score was 4.8±1.6 and the mean HAS-BLED score was 2.5±0.9. The average LAA orifice diameter was 21.7±3.4 mm, and the median implant size was 27.0 mm. The compression ratio was 15.2±6.2%. Three patients (25%) were performed under general anesthesia, nine patients (75%) were performed with local anesthesia. The average procedure time was 61.2±18.5 minutes. The average fluoroscopy time was 6.8±3.3 minutes. There was no device embolization or pericardial effusion. There was no periprocedural cerebral event, assess site bleeding, or death during hospital admission. Mild peridevice leak was observed in three patients (25%), and all had disappeared on TEE performed at the 45-day follow-up. The median length of stay was two days. Conclusion: The result of the present study showed that percutaneous LAA occlusion with the Watchman device was feasible and safe. The successfulness of the procedures and periprocedural complications were similar to standard in literature. © 2015, Medical Association of Thailand. All rights reserved.