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A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance and dysarthria that had worsened over four years and a month, respectively. Neurological exams revealed cognitive impairment, proximal weakness of the lower extremities, generalized hyperrflexia, ataxia, sensory disturbances predominant in deep sensation, urinary retention, and gait instability. On nerve conduction study, no sensory nerve action potentials were evoked in the upper and lower limbs. Since his grandmother suffered from similar symptoms, we investigated genetic analysis, which revealed a missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene. He was subsequently diagnosed with hereditary sensory and autonomic neuropathy 1E (HSAN1E). It is important to recognize that increased deep tendon reflex can be observed in HSAN1E.
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Neuropatias Hereditárias Sensoriais e Autônomas , Mutação de Sentido Incorreto , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Neuropatias Hereditárias Sensoriais e Autônomas/diagnósticoRESUMO
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. METHODS: Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants. RESULTS: We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early-onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early-onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction. INTERPRETATION: Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Doenças Neurodegenerativas , Adulto , Humanos , Demência Frontotemporal/genética , Esclerose Lateral Amiotrófica/genética , Serina C-Palmitoiltransferase/genética , Esfingolipídeos , CeramidasRESUMO
We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep-onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA-DRB1*15:01-DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1.
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INTRODUCTION: Uterine adenomyosis is a benign disorder in which endometrial glands and stroma are present within the myometrium. There have been several case reports of cerebral infarction associated with adenomyosis, but their clinical characteristics, optimal treatment, and prognosis have not been systematically reviewed. METHODS: A case of cerebral infarction with adenomyosis is reported, and a comprehensive systematic literature search using the PubMed database was conducted. RESULTS: A 42-year-old woman, previously diagnosed with adenomyosis, developed multiple cerebral infarctions during menstruation. Her CA125 level was 293 U/mL, and treatment with edoxaban 30 mg was started. Seven days after hospital discharge, she had her subsequent menstrual period and then developed a recurrent stroke. Her CA125 level was 743 U/mL on readmission. A hysterectomy was performed, and the patient has had no further stroke recurrence. A systematic review identified 19 cases with cerebral infarction associated with adenomyosis, including the present case. The patients' clinical characteristics included young age (44.7 ± 6.2 years), stroke development during menstruation (85%), multiple infarctions affecting ≥ 3 vessel territories (39%), and high levels of CA125 and D-dimer (810.6 ± 888.4 U/mL, and 10.3 ± 18.6 µg/mL, respectively). Antithrombotic therapy was given to 14 patients, but recurrent stroke occurred in 5 (36%) patients. Hysterectomy was conducted in 5 and 4 patients with initial and recurrent stokes, respectively, and there were no further recurrences thereafter. CONCLUSION: Cerebral infarction associated with adenomyosis has specific clinical characteristics. Antithrombotic therapy was insufficient, and hysterectomy should particularly be considered in cases of recurrent stroke.
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Adenomiose , AVC Embólico , Acidente Vascular Cerebral , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adenomiose/complicações , Adenomiose/diagnóstico , AVC Embólico/complicações , Fibrinolíticos , Infarto Cerebral/complicações , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Antígeno Ca-125RESUMO
A 55-year-old man presented a slowly progressive sensory disorder, predominantly in both lower limbs, and gait disturbance. Neurological examinations revealed abnormal sensation and spasticity in both lower limbs, and a wide-based gait. Although examination revealed mild hyperchloremia and decreased motor conduction velocity in the peroneal nerve, head and whole spine MRI, and spinal fluid examination were normal. His job history revealed he had been engaged in metal cleaning work using 1-bromopropane (1-BP) for three years. His serum bromide concentration was increased to 175.6 mg/l (standard value: 5 or less), so we diagnosed him as having 1-BP neurotoxicity. The serum bromide concentration decreased after avoidance of exposure to 1-BP, but the gait disturbance remained. It was considered that we should obtain a detailed job history and measure the serum bromide concentration in patients with a sensory disorder in the extremities and gait disturbance of unknown origin.
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Brometos , Síndromes Neurotóxicas , Humanos , Masculino , Pessoa de Meia-Idade , Ataxia , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Transtornos de SensaçãoRESUMO
In the field of hereditary spastic paraplegia (HSP), progress in molecular diagnostics needs to be translated into robust phenotyping studies to understand genetic and phenotypic heterogeneity and to support interventional trials. ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26, SPG15) is a rare, early-onset complex HSP, characterized by progressive spasticity and a variety of other neurological symptoms. While prior reports, often in populations with high rates of consanguinity, have established a general phenotype, there is a lack of systematic investigations and a limited understanding of age-dependent manifestation of symptoms. Here we delineate the clinical, neuroimaging and molecular features of 44 individuals from 36 families, the largest cohort assembled to date. Median age at last follow-up was 23.8 years covering a wide age range (11-61 years). While symptom onset often occurred in early childhood [median: 24 months, interquartile range (IQR) = 24], a molecular diagnosis was reached at a median age of 18.8 years (IQR = 8), indicating significant diagnostic delay. We demonstrate that most patients present with motor and/or speech delay or learning disabilities. Importantly, these developmental symptoms preceded the onset of motor symptoms by several years. Progressive spasticity in the lower extremities, the hallmark feature of HSP-ZFYVE26, typically presents in adolescence and involves the distal lower limbs before progressing proximally. Spasticity in the upper extremities was seen in 64%. We found a high prevalence of extrapyramidal movement disorders including cerebellar ataxia (64%) and dystonia (11%). Parkinsonism (16%) was present in a subset and showed no sustained response to levodopa. Cognitive decline and neurogenic bladder dysfunction progressed over time in most patients. A systematic analysis of brain MRI features revealed a common diagnostic signature consisting of thinning of the anterior corpus callosum, signal changes of the anterior forceps and non-specific cortical and cerebellar atrophy. The molecular spectrum included 45 distinct variants, distributed across the protein structure without mutational hotspots. Spastic Paraplegia Rating Scale scores, SPATAX Disability Scores and the Four Stage Functional Mobility Score showed moderate strength in representing the proportion of variation between disease duration and motor dysfunction. Plasma neurofilament light chain levels were significantly elevated in all patients (Mann-Whitney U-test, P < 0.0001) and were correlated inversely with age (Spearman's rank correlation coefficient r = -0.65, P = 0.01). In summary, our systematic cross-sectional analysis of HSP-ZFYVE26 patients across a wide age-range, delineates core clinical, neuroimaging and molecular features and identifies markers of disease severity. These results raise awareness to this rare disease, facilitate an early diagnosis and create clinical trial readiness.
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Paraplegia Espástica Hereditária , Humanos , Pré-Escolar , Paraplegia Espástica Hereditária/genética , Estudos Transversais , Diagnóstico Tardio , Proteínas/genética , MutaçãoRESUMO
This review describes cryptococcal meningoencephalitis, tuberculous meningitis, neurosyphilis, and toxoplasma encephalitis. Central nervous system infections are neurological emergencies associated with mortality or other outcomes. Therefore, early diagnosis and treatment are critical. Fungal or gondii infections are rare and affect compromised hosts who are HIV positive, have diabetes, or take immunosuppressive or anticancer drugs. Cryptococcal antigens in the serum and cerebrospinal fluid are useful for the diagnosis of cryptococcal meningoencephalitis. RPR and TPHA tests are useful for the diagnosis of neurosyphilis. Cryptococcal meningoencephalitis and tuberculous meningitis often develop into hydrocephalus, making VP shunt necessary. Antifungal drugs for cryptococcal meningitis are limited by the blood-brain barrier, making a full recovery difficult; in such situations, intraventricular antifungal treatment is required.
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Meningoencefalite , Micoses , Neurossífilis , Doenças Parasitárias , Tuberculose Meníngea , Antifúngicos/uso terapêutico , Humanos , Meningoencefalite/tratamento farmacológico , Micoses/tratamento farmacológico , Neurossífilis/tratamento farmacológico , Doenças Parasitárias/tratamento farmacológico , Tuberculose Meníngea/tratamento farmacológicoRESUMO
SPG80 is a neurodegenerative disorder characterized by a pure type of juvenile-onset hereditary spastic paraplegia and is caused by a heterozygous mutation of the UBAP1 (ubiquitin-associated protein 1) gene. UBAP1 is one of the subunits of the endosomal sorting complex required for transport I and plays a role in endosome sorting by binding to ubiquitin-tagged proteins. In this study, we generated novel Ubap1+/E176Efx23 knock-in mice, in which the SOUBA domain of Ubap1 was completely deleted with the UMA domain being intact, as an animal model of SPG80. The knock-in mice with this heterozygous Ubap1 truncated mutation appeared normal at birth, but they developed progressive hind limb dysfunction several months later. Molecular pathologically, loss of neurons in the spinal cord and accumulation of ubiquitinated proteins were observed in Ubap1+/E176Efx23 knock-in mice. In addition, changes in the distributions of Rab5 and Rab7 in the spinal cord suggest that this mutation in Ubap1 disturbs endosome-mediated vesicular trafficking. This is the first report of a mouse model that reproduces the phenotype of SPG80. Our knock-in mice may provide a clue for understanding the molecular pathogenesis underlying UBAP1-related HSP and screening of therapeutic agents.
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Proteínas de Transporte , Paraplegia Espástica Hereditária , Camundongos , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/química , Paraplegia Espástica Hereditária/genética , Endossomos/genética , Fenótipo , Modelos Animais de Doenças , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMO
A heterozygous mutation in GRID2 that causes SCAR18 was first reported in an Algerian family with autosomal dominant cerebellar ataxia (ADCA). We identified the second ADCA family with a heterozygous GRID2 mutation. The Algerian family had cognitive impairment and hearing loss associated with cerebellar ataxia. However, the Japanese family presented here showed pure cerebellar ataxia. Therefore, we should also screen for the GRID2 mutation in ADCA families with pure cerebellar ataxia.
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We herein report a 47-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) revealed by periventricular radial linear enhancement on repeated brain magnetic resonance imaging (MRI). He presented with a history of headache and a fever followed by somnolence and worsening of consciousness. On admission (16 days from the onset), although lymphocytic pleocytosis and hypoglycorrhachia in the cerebrospinal fluid (CSF) were noted, initial brain MRI demonstrated non-specific findings. At 30 days from the onset, repeated brain MRI revealed characteristic findings of GFAP-A, and we detected anti-GFAP antibodies in the CSF. Thus, repeated brain MRI provides clues for the diagnosis of GFAP-A.
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Astrócitos , Encéfalo , Astrócitos/patologia , Autoanticorpos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Proteína Glial Fibrilar Ácida , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
We report a 77-year-old woman with a thymoma, anti-LGI1antibody associated encephalitis (LGI1 encephalitis), and MG accompanied by positive anti-acetylcholine receptor antibodies (AchR Ab) and anti-titin antibodies (titin Ab). She was treated with thymomectomy followed by immunosuppressive therapy, which resulted in immediate amelioration of motor weakness and gradual improvement of cognitive impairment over the next two years. LGI1 Ab were positive at two months after thymomectomy, followed by negative conversion demonstrated on 1 year examination. The AchR Ab level had gradually decreased but titin Ab was positive on re-examination after two years, although the cognition and motor impairment symptoms had been alleviated. In patients with suspected autoimmune encephalitis, the detection of several autoantibodies including LGI1 and thymomas provides useful information for making an accurate diagnosis.
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BACKGROUND AND OBJECTIVES: Variations in SLC9A6 cause the X-linked neurologic disorder Christianson syndrome in males. Meanwhile, female carriers with SLC9A6 variations may remain asymptomatic or develop intellectual disability, behavioral problems, and psychiatric illnesses. Only a few female carriers have been reported to have associated atypical parkinsonism in late life. METHODS: We present a Japanese family with a novel SLC9A6 variation identified by quad whole-exome sequencing analysis and a reverse phenotyping strategy. The molecular and cellular impacts of the W89R variation in vitro were examined. RESULTS: The missense variation (c.265T>C, p.Trp89Arg) in SLC9A6 cosegregated with atypical parkinsonism and intellectual disability in female carriers of this family. The female carriers in this family presented with bradykinesia, rigidity, and tremor, predominately on the right side. We found that the W89R variation changed membrane traffic of NHE6-harboring vesicles, indicating potential involvement in the disease pathogenesis. DISCUSSION: This study might have revealed an example of a monogenic origin of atypical parkinsonism in females with SLC9A6 variations and draw attention to this understudied female-specific phenotype in clinical practice.
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SPG31 is an autosomal dominant hereditary spastic paraplegia caused by pathogenic variants in the receptor expression-enhancing protein 1 (REEP1) gene. We analyzed 488 DNA samples from unrelated HSP patients collected by Japan Spastic Paraplegia Research Consortium and found 15 Japanese SPG31 families. We investigated each family and found a total of 25 individuals with REEP1 variants (comprising 22 patients and three asymptomatic carriers). Fourteen REEP1 variants (five missense, three nonsense, four frameshift, one splice site, and one large deletion) including 11 novel ones were detected. Seventy percent of the patients (14 of 20) showed a pure form and the others (6 of 20) showed a complicated form with peripheral neuropathy. Fifty percent of the patients had neurological symptoms before the age of 10 and 20% of them at age 41-50. The mean age of onset was 19.6 ± 18.7 (from 5 to 67, n = 15) years for males and 32.8 ± 24.7 (from 4 to 60, n = 5) years for females. Although the difference was not statistically significant (p = 0.38, Mann-Whitney U test), males tended to have an earlier age of onset. Moreover, all three asymptomatic carriers were female. We investigated additional factors as to phenotypic appearance in one family with apparent intrafamilial variability in age at onset and clinical severity, but no additional factors including gene variants could be found. This is the first report of clinical and genetic findings of SPG31 in Japan, which may lead to further studies of the genotype-phenotype correlation of SPG31.
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Paraplegia Espástica Hereditária , Feminino , Humanos , Japão/epidemiologia , Masculino , Proteínas de Membrana Transportadoras/genética , Mutação , Fenótipo , Paraplegia Espástica Hereditária/genéticaAssuntos
Epilepsia , Doenças do Sistema Nervoso Periférico , Paraplegia Espástica Hereditária , Ataxia/complicações , Ataxia/genética , Corpo Caloso/diagnóstico por imagem , Epilepsia/complicações , Epilepsia/genética , Humanos , Mutação/genética , Paraplegia/complicações , Paraplegia/genética , Doenças do Sistema Nervoso Periférico/complicações , Paraplegia Espástica Hereditária/complicações , Paraplegia Espástica Hereditária/genética , Espastina/genéticaRESUMO
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chédiak-Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.
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Síndrome de Chediak-Higashi/genética , Mutação , Paraplegia Espástica Hereditária/genética , Proteínas de Transporte Vesicular/genética , Adulto , Síndrome de Chediak-Higashi/diagnóstico , Diagnóstico Diferencial , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/diagnóstico , Sequenciamento do Exoma/métodosRESUMO
In 2012, a 69-year-old man noticed slowness in his movements and was diagnosed with Parkinson's disease (PD). In December 2017, he was admitted to a hospital with a diagnosis of hypothermia. One month later, in January 2018, he had difficulty moving around at home and was admitted to our hospital because of impaired consciousness. On admission, his consciousness was rated as level II-10, his body temperature was 32.8â, and he was pale and had extrapyramidal symptoms. Electrocardiogram showed T-wave flattening and the first degree of atrioventricular block. Warming was started with improvement of the level of consciousness on the sixth hospital day. His cognitive function was normal (HDS-R 27/30), but the Schellong test (an orthostatic blood pressure test) showed a marked decrease in systolic blood pressure upon standing. Although sympathetic skin and flow responses were almost normal, except for low levels of basal skin blood flow, we speculated that the patient had impaired thermoregulation due to central autonomic dysfunction. In the literature, such impaired thermoregulation was suggested as the cause of hypothermia in seven patients with PD. Therefore, we recommend that patients with PD and repeated hypothermia should be instructed to maintain a suitable room temperature and to dress warmly. (Received 25 June, 2021; Accepted 31 August, 2021; Published 1 December, 2021).
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Doenças do Sistema Nervoso Autônomo , Doenças dos Gânglios da Base , Hipotermia , Doença de Parkinson , Idoso , Humanos , Hipocinesia , Hipotermia/etiologia , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/terapiaRESUMO
BACKGROUND: Spastic paraplegia type 4 (SPG4) is caused by mutations in the SPAST gene, is the most common form of autosomal-dominant pure hereditary spastic paraplegias (HSP), and is rarely associated with a complicated form that includes ataxia, epilepsy, and cognitive decline. To date, the genotype-phenotype correlation has not been substantially established for SPAST mutations. CASE PRESENTATION: We present a Japanese patient with infantile-onset HSP and a complex form with coexisting ataxia and epilepsy. The sequencing of SPAST revealed a de novo c.1496G > A (p.R499H) mutation. A review of the literature revealed 16 additional patients with p.R499H mutations in SPAST associated with an early-onset complicated form of HSP. We found that the complicated phenotype of patients with p.Arg499His mutations could be mainly divided into three subgroups: (1) infantile-onset ascending hereditary spastic paralysis, (2) HSP with severe dystonia, and (3) HSP with cognitive impairment. Moreover, the c.1496G > A mutation in SPAST may occur as a de novo variant at noticeably high rates. CONCLUSION: We reviewed the clinical features of the patients reported in the literature with the p.Arg499His mutation in SPAST and described the case of a Japanese patient with this mutation presenting a new complicated form. Accumulating evidence suggests a possible association between infantile-onset complicated HSP and the p.Arg499His mutation in SPAST. The findings of this study may expand the clinical spectrum of the p.Arg499His mutation in SPAST and provide an opportunity to further study the genotype-phenotype correlation of SPG4.
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Paraplegia Espástica Hereditária , Humanos , Mutação/genética , Paraplegia/genética , Fenótipo , Paraplegia Espástica Hereditária/genética , Espastina/genéticaRESUMO
We report here a rare case of adult-onset multiloculated hydrocephalus (MLH) after Cryptococcal meningitis. A 63-year-old man had Cryptococcal ventriculitis in 2011, and he recovered with treatment of antimycotic drugs. However, he was admitted again because of disorientation and amnesia, and brain MRI showed dilation of the inferior horn of the left lateral ventricle. He underwent a ventriculoperitoneal shunt (VPS) for noncommunicating hydrocephalus in 2019, and the disorientation and amnesia improved. One year after the VPS, he was admitted because of urinary dysfunction and gait disturbance. Brain MRI showed dilation of the bilateral anterior horns of the lateral ventricles. He underwent an additional VPS into the space in 2020, and urinary dysfunction and gait disturbance improved. This case was supposed that the symptom in agreement with the dilated ventricle by MLH was shown.
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Ventriculite Cerebral , Hidrocefalia , Meningite Criptocócica , Amnésia , Ventriculite Cerebral/diagnóstico por imagem , Ventriculite Cerebral/tratamento farmacológico , Ventriculite Cerebral/etiologia , Confusão , Encefalite , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Masculino , Pessoa de Meia-Idade , Mielite , NeoplasiasRESUMO
Familial dementia is a rare inherited disease involving progressive impairment of memory, thinking, and behavior. We report a novel heterozygous pathogenic variant (c.199Gâ>âA, p.Val67Ile) in the CIAO1 gene that appears to be co-segregated with Alzheimer's disease in a Japanese family. Biochemical analysis of CIAO1 protein revealed that the variant increases the interaction of CIAO1 with immature amyloid-ß protein precursor (AßPP), but not mature or soluble AßPP, indicating plausible CIAO1 involvement in AßPP processing. Our study indicates that a heterozygous variant in the CIAO1 gene may be closely related to autosomal dominant familial dementia.
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Doença de Alzheimer , Precursor de Proteína beta-Amiloide/genética , Metalochaperonas/genética , Mutação de Sentido Incorreto/genética , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Encéfalo/patologia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Japão , Masculino , NeuroimagemRESUMO
We herein describe a Charcot-Marie-Tooth disease (CMT) family with a MFN2 mutation with atypical ocular manifestations. The proband, his mother, his third daughter, and his deceased maternal grandfather all had symptoms of CMT and a visual impairment (either cataracts or severe astigmatism). On whole-exome sequencing for the proband having CMT and congenital cataracts, we identified a c.314C>T (p.Thr105Met) mutation in MFN2, but no mutation in the causative genes associated with cataracts. This missense mutation in MFN2 co-segregated with CMT and the atypical ocular manifestations in this family. The findings of this study might help to expand the clinical phenotype of heterogeneous MFN2-related CMT.