RESUMO
A pool boiling phenomenon referred to as secondary boiling effects is discussed. Based on the experimental trends, a mechanism is proposed that identifies the parameters that lead to this phenomenon. Secondary boiling effects refer to a distinct decrease in the wall superheat temperature near the critical heat flux due to a significant increase in the heat transfer coefficient. Recent pool boiling heat transfer experiments using femtosecond laser processed Inconel, stainless steel, and copper multiscale surfaces consistently displayed secondary boiling effects, which were found to be a result of both temperature drop along the microstructures and nucleation characteristic length scales. The temperature drop is a function of microstructure height and thermal conductivity. An increased microstructure height and a decreased thermal conductivity result in a significant temperature drop along the microstructures. This temperature drop becomes more pronounced at higher heat fluxes and along with the right nucleation characteristic length scales results in a change of the boiling dynamics. Nucleation spreads from the bottom of the microstructure valleys to the top of the microstructures, resulting in a decreased surface superheat with an increasing heat flux. This decrease in the wall superheat at higher heat fluxes is reflected by a "hook back" of the traditional boiling curve and is thus referred to as secondary boiling effects. In addition, a boiling hysteresis during increasing and decreasing heat flux develops due to the secondary boiling effects. This hysteresis further validates the existence of secondary boiling effects.
Assuntos
Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Epilepsia/diagnóstico , Epilepsia/terapia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/terapia , Doença Catastrófica/terapia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Ciclismo/lesões , Vértebras Cervicais/lesões , Fraturas da Coluna Vertebral/diagnóstico , Pinos Ortopédicos , Vértebras Cervicais/cirurgia , Pré-Escolar , Diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Fixação Interna de Fraturas/métodos , Humanos , Imageamento por Ressonância Magnética , Fraturas da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological diseases affecting both the central and the peripheral nervous systems. They are characterized by autosomal recessive inheritance, progressive ataxia and degeneration of the cerebellum and spinal cord. Onset is generally before the third decade of life. The most frequent of these rare disorders in the Caucasian population is Friedreich's ataxia followed by ataxias with oculomotor apraxia. ARCAs are caused by mutations at specific loci but not every affected gene is known to date. Clinical diagnosis can be confirmed by ancillary tests (biochemical, neuroimaging and electrophysiological investigations) and mutation analyses if the causative gene has been identified. Correct clinical and genetic diagnosis is necessary for prognosis, genetic counseling and pharmacological treatment. For the majority of ARCAs a curative treatment is not available.
Assuntos
Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Genes Recessivos/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , HumanosRESUMO
We present the case of a 13-month-old girl with a right occipital cortical alteration on MRI that proved to be a growing lesion. Tumor growth had been observed over a period of 15 months before total resection was performed, revealing a dysembryoplastic neuroepithelial tumor WHO grade I. This case shows that dysembryoplastic neuroepithelial tumors can present as growing neoplasias. It underlines the importance of obtaining histologic diagnosis and close follow-up examinations using MRI, even in so-called stable lesions that are only unveiling through epileptic seizures.
Assuntos
Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/patologia , Biópsia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Progressão da Doença , Epilepsia/etiologia , Feminino , Humanos , Lactente , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/cirurgiaRESUMO
Ataxia with oculomotor apraxia type 2 (AOA2), a neurodegenerative disorder with juvenile to adolescent onset is caused by mutations within the SENATAXIN gene ( SETX). We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. Sequencing the 24 coding exons and flanking intronic sequences revealed 11 novel DNA variations, including seven unknown missense mutations, a dinucleotide deletion, a four-nucleotide deletion affecting the 5' splice site of exon 22 and two sequence variations, which are considered to be polymorphisms. By molecular testing the clinical diagnosis has been confirmed in all patients.
Assuntos
Apraxias/genética , Ataxia Cerebelar/genética , Análise Mutacional de DNA , Doenças do Nervo Oculomotor/genética , RNA Helicases/genética , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Alelos , Apraxias/sangue , Apraxias/diagnóstico , Atrofia , Ataxia Cerebelar/sangue , Ataxia Cerebelar/diagnóstico , Cerebelo/patologia , Deleção Cromossômica , Consanguinidade , DNA Helicases , Éxons/genética , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Enzimas Multifuncionais , Mutação de Sentido Incorreto , Exame Neurológico , Doenças do Nervo Oculomotor/sangue , Fenótipo , Polimorfismo Genético/genética , Adulto JovemRESUMO
Autosomal recessive cerebellar ataxias are a phenotypically and genetically heterogeneous group of diseases. Major forms can be distinguished on the basis of clinical signs, age of onset, biochemical parameters or genotypes. To develop rational diagnostic strategies, phenotypic information, e.g., age of onset combined with population-specific disease frequencies could be highly favourable. We tested this hypothesis for single candidate loci and mutations in North European ataxia patients with juvenile and early adult onset. While we could prove that Friedreich ataxia (FRDA) is frequent in Germany, only few patients with ataxia-oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) were diagnosed. The frequency of the mitochondrial recessive ataxia syndrome (MIRAS) and the infantile onset spinocerebellar ataxia (IOSCA) in this population remains unknown since no case with the common mutation of the corresponding gene was detected.
Assuntos
Ataxia/epidemiologia , Ataxia/genética , Genes Recessivos , Adolescente , Adulto , Idade de Início , Ataxia/classificação , Criança , DNA Helicases , Análise Mutacional de DNA , DNA Polimerase gama , Proteínas de Ligação a DNA/genética , DNA Polimerase Dirigida por DNA/genética , Feminino , Humanos , Proteínas de Ligação ao Ferro/genética , Masculino , Pessoa de Meia-Idade , Enzimas Multifuncionais , Proteínas Nucleares/genética , Proteínas/genética , RNA Helicases/genética , RNA Longo não Codificante , FrataxinaRESUMO
The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a clinically and genetically heterogeneous group of neurodegenerative disorders. To date 27 different loci have been identified for these conditions. Recently, two deletions as well as one missense mutation in the beta-III spectrin gene (STBN2) were identified causing SCA5. To evaluate the clinical relevance of these mutations, we screened 310 familial and sporadic patients with ataxia. While none of the individuals tested had evidence for one of the known SCA5 mutations, additional sequencing of the coding region for 22 unrelated patients revealed three novel missense exchanges at evolutionary conserved amino acid positions. Even though each variation marks a unique genotype in 250 alleles, a disease causing capacity can be excluded with high probability. These results reflect the challenges for molecular analyses in SCA5.
Assuntos
Testes Genéticos , Espectrina/genética , Ataxias Espinocerebelares/genética , Alelos , Éxons , Feminino , Frequência do Gene , Testes Genéticos/métodos , Alemanha/epidemiologia , Humanos , Masculino , Mutação , Ataxias Espinocerebelares/epidemiologiaRESUMO
BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is associated with an expansion of CAG/CAA trinucleotide repeats in the gene encoding the TATA-binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity. METHODS: Eye movements (saccades, smooth pursuit) of 15 SCA17 mutation carriers (mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age-matched control subjects using the video-based two-dimensional EYELINK II system. RESULTS: Smooth pursuit initiation (step-ramp paradigm) and maintenance were strongly impaired, i.e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch-up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze-evoked nystagmus was found in one-third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades (52%) and memory-guided saccades (42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration. CONCLUSIONS: Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging (morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e.g., dementia and parkinsonism.
Assuntos
Encéfalo/fisiopatologia , Predisposição Genética para Doença/genética , Mutação/genética , Transtornos da Motilidade Ocular/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia , Proteína de Ligação a TATA-Box/genética , Adulto , Encéfalo/patologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Análise Mutacional de DNA , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/patologia , Movimentos Sacádicos/fisiologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologiaRESUMO
Albinism comprises a heterogeneous group of nonprogressive genetic disorders characterized by the absence of pigmentation in the skin, hair, and/or eyes. Hypopigmentation or complete lack of pigmentation is caused by an enzyme deficiency involving the production, metabolism, or distribution of melanin. Clinically, oculocutaneous and ocular types, as well as syndromes associated with albinism resulting from mutations in at least 14 genes, are distinguishable. Most frequent is oculocutaneous albinism (OCA), which is subdivided nowadays into four forms, OCA 1-OCA 4. OCA is inherited as an autosomal recessive trait. Clinical differentiation of OCA types is difficult due to the observed range of phenotypic variation. Thus, genetic analysis may be helpful with respect to a precise diagnosis. Sequencing of the four genes associated with OCA detects variations in approximately 60-70% of German patients with albinism. The majority of German patients are affected by OCA 1 resulting from mutations in the gene for tyrosinase, the key enzyme in the synthesis of melanin pigment. Worldwide, OCA2 is the most frequent form of albinism.
Assuntos
Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/prevenção & controle , Genes Recessivos/genética , Aconselhamento Genético/métodos , Predisposição Genética para Doença/genética , Monofenol Mono-Oxigenase/genética , Albinismo Oculocutâneo/diagnóstico , Humanos , Medição de RiscoAssuntos
Atrofia/fisiopatologia , Doenças Cerebelares/fisiopatologia , Cerebelo/fisiopatologia , Distúrbios Distônicos/fisiopatologia , Predisposição Genética para Doença/genética , Adulto , Atrofia/genética , Atrofia/metabolismo , Ataxia Cerebelar/genética , Ataxia Cerebelar/metabolismo , Ataxia Cerebelar/fisiopatologia , Doenças Cerebelares/genética , Doenças Cerebelares/metabolismo , Cerebelo/metabolismo , Cerebelo/patologia , Distúrbios Distônicos/genética , Distúrbios Distônicos/metabolismo , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Mutação/genética , Fenótipo , Proteína de Ligação a TATA-Box/genética , Distúrbios da Voz/genética , Distúrbios da Voz/metabolismo , Distúrbios da Voz/fisiopatologiaRESUMO
We present the operation of an optical device that exhibits diodelike properties based on two adjacent layers of quantum dots (QDs) encased in a fiber-optic jacket. The possibility of a multilayered device is also discussed. A significant change in the emission spectrum of CdSe/ZnS core-shell QDs was observed when excited by the input laser and the fluorescence of other CdSe/ZnS core-shell QDs. The output of the diode can be taken to be either the incoming laser wavelength of light similar to a conventional diode, or the output may be considered to be one of the QD fluorescence wavelengths. Current work has applications in biological fluorescence monitors and sensors as well as in telecommunications applications.
RESUMO
Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.
Assuntos
Ataxias Espinocerebelares/patologia , Adulto , Atrofia , Gânglios da Base/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Cerebelo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Testes Neuropsicológicos , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/patologia , Paraplegia Espástica Hereditária/patologia , Paraplegia Espástica Hereditária/fisiopatologia , Paraplegia Espástica Hereditária/psicologia , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/psicologia , Telencéfalo/patologia , Fatores de TempoRESUMO
Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.
Assuntos
Tronco Encefálico/patologia , Cerebelo/patologia , Degeneração Neural/patologia , Neurônios/patologia , Ataxias Espinocerebelares/patologia , Idoso , Doenças Auditivas Centrais/genética , Doenças Auditivas Centrais/patologia , Doenças Auditivas Centrais/fisiopatologia , Tronco Encefálico/fisiopatologia , Cerebelo/fisiopatologia , Análise Mutacional de DNA , Transtornos de Deglutição/genética , Transtornos de Deglutição/patologia , Transtornos de Deglutição/fisiopatologia , Feminino , Genótipo , Alemanha , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação/genética , Degeneração Neural/fisiopatologia , Transtornos da Motilidade Ocular/genética , Transtornos da Motilidade Ocular/patologia , Transtornos da Motilidade Ocular/fisiopatologia , Linhagem , Peptídeos/genética , Transtornos de Sensação/genética , Transtornos de Sensação/patologia , Transtornos de Sensação/fisiopatologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Expansão das Repetições de Trinucleotídeos/genéticaAssuntos
Adenosina Trifosfatases/genética , Códon sem Sentido , Paraplegia/genética , Linhagem , Adulto , Cromossomos Humanos Par 2 , Análise Mutacional de DNA/métodos , Éxons , Feminino , Alemanha/epidemiologia , Humanos , Leucina/genética , Masculino , Pessoa de Meia-Idade , Paraplegia/epidemiologia , EspastinaRESUMO
Friedreich's ataxia (FRDA), the most common autosomal recessively inherited ataxia, is due to a homozygous GAA triplet repeat expansion in the first intron of the FRDA gene in about 96% of patients. Approximately 4% of FRDA patients are compound heterozygotes with a GAA repeat expansion in one allele and a point mutation in the coding region of the second allele. To reinvestigate the mutation spectrum, we searched for mutations including exon deletions in six patients heterozygous for the GAA repeat expansion and found two unknown missense mutations, p.Asn146Lys and p.Leu186Arg, in trans to the expanded FRDA allele. Interestingly, we detected a heterozygous 2776 bp deletion including exon 5a in one of our patients. This deletion removes 50 of the 210 residues of the frataxin. Furthermore, since no FRDA case with two-point mutations is known, we screened eight patients with FRDA phenotype but GAA alleles within the normal range but did not reveal a mutation within the FRDA gene. In addition, DNA polymorphisms have been found in four out of 100 control individuals in this study.
Assuntos
Sequência de Bases , Éxons , Ataxia de Friedreich/genética , Mutação de Sentido Incorreto , Deleção de Sequência , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Masculino , LinhagemAssuntos
Síndrome de Creutzfeldt-Jakob/genética , Expansão das Repetições de DNA , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Alelos , Encéfalo/patologia , Comorbidade , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Alemanha/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/epidemiologiaRESUMO
The authors report a German family with autosomal dominant cerebellar ataxia tightly linked to the spinocerebellar ataxia type 5 (SCA5) locus (multipoint lod score 5.76). The phenotype is characterized by a purely cerebellar syndrome with a downbeat nystagmus occurring prior to the development of other features. Imaging studies demonstrated cortical cerebellar atrophy. Progression is slow even in patients with a disease onset during the second decade. The age at onset varies from 15 to 50 years.
Assuntos
Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/genética , Adolescente , Adulto , Cromossomos Humanos Par 11/genética , Progressão da Doença , Feminino , Genes Dominantes , Alemanha/epidemiologia , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/epidemiologia , Nistagmo Patológico/genética , Linhagem , Espectrina , Ataxias Espinocerebelares/epidemiologiaRESUMO
The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Multiple system atrophy is also a sporadic neurodegenerative disorder of unknown origin that may cause prominent cerebellar symptoms (MSA-C). The final neuropathological answer to the question whether IDCA-P and MSA-C represent different varieties of one disease or two distinct entities is still lacking. Three-dimensional MRI-based volumetry allows morphological investigations intra vitam. Volumetric analysis of cerebellum, brainstem and basal ganglia was therefore performed in 46 patients with sporadic cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia were excluded from the study since cognitive impairment is an exclusion criterion for the diagnosis of MSA. Cerebellar patients were clinically divided into two groups: 33 patients with multiple system atrophy with prominent cerebellar symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both cerebellar groups while additional brainstem atrophy was significantly more pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to be restricted to single MSA-C individuals while group comparisons of mean volumes did not yield significant differences from controls. Based on the volumetric data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and 100% of IDCA-P individuals. The finding of specific imaging characteristics strengthens (i) the value of MRI volumetry in separating MSA-C from other types of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent neurodegenerative disorders in MSA-C and IDCA-P.
Assuntos
Ataxia Cerebelar/diagnóstico , Atrofia de Múltiplos Sistemas/diagnóstico , Adulto , Idoso , Análise de Variância , Tronco Encefálico/patologia , Núcleo Caudado/patologia , Cefalometria/métodos , Ataxia Cerebelar/patologia , Cerebelo/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Putamen/patologia , Fatores de TempoRESUMO
An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.