Publications by authors named "Akiko Yoshimura"

Background: Despite the risk of respiratory depression, benzodiazepines are often prescribed to patients receiving palliative care owing to their efficacy in symptom control. Opioids, which also cause respiratory depression, are often administered to patients with advanced-stage cancer. However, the additive effect of the two drugs has not been systematically analyzed.

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Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled.

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Article Synopsis
  • * Researchers screened 1555 Japanese IPN patients for CGG repeat expansions using advanced techniques, finding 44 cases with this genetic marker, making it a common cause of the condition.
  • * The findings underscore the importance of tailored screening strategies in clinical settings, particularly for identifying Charcot-Marie-Tooth disease (CMT) cases linked to CGG repeat expansions.
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Background: Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in surrounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration.

Methodology/principal Findings: The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations.

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Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.

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  • The study investigates the genetic causes of late-onset cerebellar ataxia in Japan, focusing on GAA repeat expansions in the FGF14 gene.
  • Analysis of 940 patients revealed pathogenic FGF14 GAA repeat expansions in 12 patients, with a median size of 309 repeats and an average age of onset of nearly 67 years.
  • The findings suggest that FGF14 GAA repeat analysis is crucial for diagnosing cerebellar ataxia, especially in cases with episodic symptoms or normal MRI results, enhancing the understanding of this genetic disorder.
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Background And Objective: Biallelic mutations in the COA7 gene have been associated with spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3), and a notable clinical diversity has been observed. We aim to identify the genetic and phenotypic spectrum of COA7-related disorders.

Methods: We conducted comprehensive genetic analyses on the COA7 gene within a large group of Japanese patients clinically diagnosed with inherited peripheral neuropathy or cerebellar ataxia.

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Background And Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan.

Methods: We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL.

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  • The study investigates the genetic causes of early-onset painful peripheral neuropathies related to the SCN9A gene and Nav1.7 sodium channels, focusing on conditions like erythromelalgia and paroxysmal extreme pain disorder.
  • Researchers sequenced 18 related genes in eight patients, discovering four specific mutations in the SCN9A gene, including a novel mutation (F1624S).
  • Electrophysiological tests confirmed that the F1624S mutation caused significant changes in the behavior of Nav1.7 channels, which helps explain how these mutations contribute to different pain disorders linked to SCN9A.
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Human T lymphotropic virus type 1-assoicated (HTLV-1-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disease caused by the persistent proliferation of HTLV-1-infected T cells. Here, we performed a T cell receptor (TCR) repertoire analysis focused on HTLV-1-infected cells to identify and track the infected T cell clones that are preserved in patients with HAM/TSP and migrate to the CNS. TCRβ repertoire analysis revealed higher clonal expansion in HTLV-1-infected cells compared with noninfected cells from patients with HAM/TSP and asymptomatic carriers (ACs).

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Article Synopsis
  • - The study investigates GGC repeat expansions in relation to inherited peripheral neuropathies (IPNs), aiming to clarify the clinical and genetic features of these conditions, which have been understudied.
  • - Researchers analyzed 1783 Japanese patients diagnosed with IPN/Charcot-Marie-Tooth disease (CMT) and found repeat expansions in 26 cases, revealing a median age of onset of 32.7 years and a predominance of intermediate CMT.
  • - The findings highlight the clinical diversity of these diseases, including symptoms like dysautonomia, and underscore the importance of genetic screening for early diagnosis, especially in Asian patients with specific clinical characteristics.
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  • Genetic factors are identified as the primary cause of periodic paralysis, and the study aimed to uncover these genetic causes specifically in Japan.
  • A comprehensive analysis was performed on 119 Japanese patients suspected of having periodic paralysis, resulting in the detection of 25 genetic variants linked to the condition.
  • The study found that a higher diagnostic rate was associated with factors like family history, younger onset age, and the frequency of paralytic attacks, indicating the genetic complexity of periodic paralysis in this population.
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Non-coding repeat expansions within and genes have lately been linked to multisystem neurodegenerative diseases, which also shed light on yet undiagnosed patients with inherited peripheral neuropathies. The aim of this study was to identify the genetic basis of patients with hereditary sensory and autonomic neuropathy (HSAN). We collected 79 unrelated DNA samples clinically suspected with HSAN from multiple regions of Japan.

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The recessive intronic pentanucleotide repeat AAGGG expansion of replication factor complex subunit 1 () is associated with cerebellar ataxia, sensory neuropathy, and vestibular areflexia syndrome. And the clinical spectrum has been continuously expanding. We conducted this study to demonstrate the clinical and genetic features of a large-scale case series of Japanese patients with cerebellar ataxia with repeat expansions.

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  • * Researchers analyzed data from 71 out of 88 families diagnosed with NDM, finding various pathogenic or likely pathogenic gene variants, with 11 novel ones discovered.
  • * The study revealed that patients with SCN4A variants experience symptoms at a younger age and have different clinical features compared to those with CLCN1 variants, enriching the understanding of genetic differences in NDM.
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  • A study analyzed 2,695 cases of inherited peripheral neuropathies (IPNs) in Japan to uncover genetic factors linked to the condition, particularly focusing on large genomic variants.
  • Genetic testing techniques, including DNA microarrays and next-generation sequencing, were used to identify pathogenic variants in 909 cases, revealing specific genes responsible for different onset types and subtypes of IPN.
  • The findings aim to improve genetic testing strategies and early diagnosis for patients by detailing the genetic characteristics and clinical implications of IPNs.
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Background: Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early-onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear.

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Background: Biallelic POLR3B mutations cause a rare hypomyelinating leukodystrophy. De novo POLR3B heterozygous mutations were recently associated with afferent ataxia, spasticity, variable intellectual disability, and epilepsy, and predominantly demyelinating sensorimotor peripheral neuropathy.

Methods: We performed whole-exome sequencing (WES) of DNA samples from 804 Charcot-Marie-Tooth (CMT) cases that could not be genetically diagnosed by DNA-targeted resequencing microarray using next-generation sequencers.

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Mitochondrial disorders are a group of clinically and genetically heterogeneous multisystem disorders and peripheral neuropathy is frequently described in the context of mutations in mitochondrial-related nuclear genes. This study aimed to identify the causative mutations in mitochondrial-related nuclear genes in suspected hereditary peripheral neuropathy patients. We enrolled a large Japanese cohort of clinically suspected hereditary peripheral neuropathy patients who were mutation negative in the prescreening of the known Charcot-Marie-Tooth disease-causing genes.

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Purpose: Wolfram syndrome is a rare genetic disorder characterized by juvenile onset of diabetes mellitus with bilateral optic atrophy. We report a case of adult onset Wolfram syndrome with diabetes mellitus at age 22 and optic atrophy after age 40. The WFS1 gene sequence was analyzed in the patient and her father.

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Background And Aims: Mutations in neurofilament genes have been linked to several neuromuscular disorders. The neurofilament heavy (NEFH) gene was identified as the causative gene of Charcot-Marie-Tooth disease type 2CC (CMT2CC) in 2016, with a toxic gain of function mechanism caused by the translation and aggregation of cryptic amyloidogenic element (CAE) in the 3' untranslated region (UTR). But the NEFH-related clinical and genetic spectrums are still unclear in Japan.

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Background And Aims: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments.

Methods: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489).

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Charcot-Marie-Tooth disease (CMT) is a common hereditary peripheral polyneuropathy encompassing distinct monogenetic disorders. Pathogenic mutations in mitofusin 2 (MFN2) are the most frequent cause of its axonal type, CMT type 2A, with diverse phenotypes. We herein report a Japanese patient with a novel heterozygous MFN2 pathogenic variant (c.

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Background: Granulomatous amoebic encephalitis (GAE) is an infrequent and fatal infectious disease worldwide. Antemortem diagnosis in this condition is very difficult because clinical manifestations and neuroimaging are nonspecific.

Case Presentation: A 60-year-old Japanese woman was admitted with a chief complaint of left homonymous hemianopsia.

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Article Synopsis
  • The study investigates the prevalence of fragile X-associated tremor/ataxia syndrome (FXTAS) in Japanese patients with cerebellar ataxia, finding a prevalence of 0.3%.
  • Out of 1328 patients screened, only three (one female and two males) were identified with FMR1 premutation meeting FXTAS criteria, highlighting its rarity in Japan.
  • The clinical characteristics of these patients were unique, with notable MRI findings and one case resembling multiple system atrophy, emphasizing the need for awareness of FXTAS in ataxia cases.
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