記述言語：英語   掲載種別：研究論文（学術雑誌）  

Investigating functional, temporal, and cell-type expression features of mutations is important for understanding a complex disease. Here, we collected and analyzed common variants and de novo mutations (DNMs) in schizophrenia (SCZ). We collected 2,636 missense and loss-of-function (LoF) DNMs in 2,263 genes across 3,477 SCZ patients (SCZ-DNMs). We curated three gene lists: (a) SCZ-neuroGenes (159 genes), which are intolerant to LoF and missense DNMs and are neurologically important, (b) SCZ-moduleGenes (52 genes), which were derived from network analyses of SCZ-DNMs, and (c) SCZ-commonGenes (120 genes) from a recent GWAS as reference. To compare temporal gene expression, we used the BrainSpan dataset. We defined a fetal effect score (FES) to quantify the involvement of each gene in prenatal brain development. We further employed the specificity indexes (SIs) to evaluate cell-type expression specificity from single-cell expression data in cerebral cortices of humans and mice. Compared with SCZ-commonGenes, SCZ-neuroGenes and SCZ-moduleGenes were highly expressed in the prenatal stage, had higher FESs, and had higher SIs in fetal replicating cells and undifferentiated cell types. Our results suggested that gene expression patterns in specific cell types in early fetal stages might have impacts on the risk of SCZ during adulthood.

DOI： 10.1002/ajmg.b.32932

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記述言語：英語  

BACKGROUND: Heterozygous KCNQ2 variants cause benign familial neonatal seizures and early-onset epileptic encephalopathy in an autosomal dominant manner; the latter is called KCNQ2 encephalopathy. No case of KCNQ2 encephalopathy with arthrogryposis multiplex congenita has been reported. Furthermore, early-onset scoliosis and opisthotonus have not been documented as characteristics of KCNQ2 encephalopathy. CASE REPORT: A male infant born with scoliosis and arthrogryposis multiplex congenita developed intractable epilepsy on the second day of life. At 4 months of age, he developed opisthotonus. The opisthotonus was refractory to medication in the beginning, and it spontaneously disappeared at 8 months of age. Whole-exome sequencing revealed a novel de novo heterozygous variant in KCNQ2, NM_172107.4:c.839A > C, p.(Tyr280Ser). CONCLUSIONS: Early-onset scoliosis, arthrogryposis multiplex congenita, and opisthotonus may be related to KCNQ2 encephalopathy.

DOI： 10.1016/j.braindev.2022.12.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Drosophila behavior/human splicing protein family is involved in numerous steps of gene regulation. In humans, this family consists of three proteins: SFPQ, PSPC1, and NONO. Hemizygous loss-of-function (LoF) variants in NONO cause a developmental delay with several complications (e.g., distinctive facial features, cardiac symptoms, and skeletal symptoms) in an X-linked recessive manner. Most of the reported variants have been LoF variants, and two missense variants have been reported as likely deleterious but with no functional validation. We report three individuals from two families harboring an identical missense variant that is located in the nuclear localization signal, NONO: NM_001145408.2:c.1375C > G p.(Pro459Ala). All of them were male and the variant was inherited from their asymptomatic mothers. Individual 1 was diagnosed with developmental delay and cardiac phenotypes (ventricular tachycardia and dilated cardiomyopathy), which overlapped with the features of reported individuals having NONO LoF variants. Individuals 2 and 3 were monozygotic twins. Unlike in Individual 1, developmental delay with autistic features was the only symptom found in them. A fly experiment and cell localization experiment showed that the NONO variant impaired its proper intranuclear localization, leading to mild LoF. Our findings suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.

DOI： 10.1038/s41598-023-27770-6

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole-exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin-1 heavy chain: two with c.272A>G:p.(Lys91Arg), one with c.584C>A:p.(Thr195Lys), and the other with c.701G>T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.

DOI： 10.1111/cge.14133

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size. METHODS: We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons. Second, we compiled a comprehensive list of de novo single-nucleotide variants (SNVs) in 41,165 individuals and de novo CNVs in 3675 individuals with NDDs by aggregating our own and publicly available datasets, including denovo-db and the Deciphering Developmental Disorders study data. Third, summing up the de novo CNV rates that we estimated and SNV rates previously established, gene-based enrichment of de novo deleterious SNVs and CNVs were assessed in the 41,165 cases. Significantly enriched genes were further prioritized according to their similarity to known NDD genes using a deep learning model that considers functional characteristics (e.g., gene ontology and expression patterns). RESULTS: We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3). Among the 52 genes, we reasonably excluded 18 genes [a number almost identical to the theoretically expected false positives (i.e., 380 × 0.05 = 19)] given their constraints against deleterious variants and extracted 34 "plausible" candidate genes. Their validity as NDD genes was consistently supported by their similarity in function and gene expression patterns to known NDD genes. Quantifying the overall similarity using deep learning, we identified 11 high-confidence (> 90% true-positive probabilities) candidate genes: HDAC2, SUPT16H, HECTD4, CHD5, XPO1, GSK3B, NLGN2, ADGRB1, CTR9, BRD3, and MARK2. CONCLUSIONS: We identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes.

DOI： 10.1186/s13073-022-01042-w

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記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞産婦人科におけるリクルートは全国単位/地域単位/大学・施設単位の3階層において行われている。このうち地域単位のリクルートはほか2者と比較し,一般的ではない。神奈川県では地域単位のリクルートとして2010年から活動を継続的に行ってきた。その結果,若手医師の連携が自然に強化され,より広く若手医師が主体となって活動できる場,神奈川県若手産婦人科医の会(KTOG)の発足に至った。地域単位のリクルート活動は,全国単位/施設単位のリクルート活動を補完する機能をもち,若手医師の企画実行力やリーダーシップ育成の場所としても有用である。一方,限られた人材や予算など,全国単位のリクルート活動にはない課題も存在する。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Heterozygous variants in CLTC, which encode the clathrin heavy chain protein, cause neurodevelopmental delay of varying severity, and often accompanied by dysmorphic features, seizures, hypotonia, and ataxia. To date, 28 affected individuals with CLTC variants have been reported, although their phenotypes have not been fully elucidated. Here, we report three novel de novo CLTC (NM_001288653.1) variants in three individuals with previously unreported clinical symptoms: c.3662_3664del:p.(Leu1221del) in individual 1, c.2878T>C:p.(Trp960Arg) in individual 2, and c.2430+1G>T:p.(Glu769_Lys810del) in individual 3. Consistent with previous reports, individuals with missense or small in-frame variants were more severely affected. Unreported symptoms included a brain defect (cystic lesions along the lateral ventricles of the brain in individuals 1 and 3), kidney findings (high-echogenic kidneys in individual 1 and agenesis of the left kidney and right vesicoureteral reflux in individual 3), respiratory abnormality (recurrent pneumonia in individual 1), and abnormal hematological findings (anemia in individual 1 and pancytopenia in individual 3). Of note, individual 1 even exhibited prenatal abnormality (fetal growth restriction, cystic brain lesions, high-echogenic kidneys, and a heart defect), suggesting that CLTC variants should be considered when abnormal prenatal findings in multiple organs are detected.

DOI： 10.1038/s10038-021-00957-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic conditions in humans, including the brain, eyes, kidneys, muscles, and other organs at any age. Brain imaging shows a wide spectrum of abnormalities, including porencephaly, schizencephaly, polymicrogyria focal cortical dysplasia, periventricular leukoencephalopathy, ventricular dysmorphisms, and multiple brain calcifications. However, there are no reports in the literature showing progressive radiological findings in consecutive follow-up scans. Herein, we report three cases of COL4A1 mutations with porencephaly from gestation to five years of age or longer, and describe their clinical and brain imaging findings. CASE REPORTS: We retrospectively reviewed the clinical symptoms and radiological findings, including brain magnetic resonance imaging (MRI) and computed tomography (CT), in three female patients with COL4A1 mutations. Their mutations were c.4843G>A (p.Glu1615Lys), c.1835G>A (p.Gly612Asp), and c.3556+1G>T respectively. All the three cases represented porencephaly in the fetal period; severe hemolytic anemia in the neonatal period; and drug-resistant epilepsy, global developmental delay, and spastic quadriplegia in their childhood. RESULTS: Brain MRI and CT showed progressive white matter atrophy from gestation to five-year follow-up or later. Minor cerebral hemorrhage without symptoms occasionally occurred in one patient. Despite brain changes, the clinical picture was stable during early childhood. CONCLUSIONS: COL4A1 mutations may cause progressive cerebral atrophy beyond early childhood.

DOI： 10.1016/j.braindev.2021.06.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

DOI： 10.1136/jmedgenet-2020-106896

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe two patients with NSD1 deletion, who presented with early-onset, or recurrent cerebrovascular diseases (CVDs). A 39-year-old female showed developmental delay and abnormal gait in infancy, and developed slowly-progressive intellectual disability and movement disorders. Brain imaging suggested recurrent parenchymal hemorrhages. A 6-year-old male had tremor as a neonate and brain imaging revealed subdural hematoma and brain contusion. This report suggests possible involvement of CVDs associated with NSD1 deletion.

DOI： 10.1038/s41439-021-00151-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

DOI： 10.1016/j.ajhg.2021.01.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.

DOI： 10.1002/humu.24130

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.

DOI： 10.1002/humu.24129

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To describe beneficial effects of callosotomy on KCNQ2-related intractable epilepsy. CASE REPORT: Our patient was a 10-year-old girl who had developed epilepsy during the neonatal period, accompanied by a suppression-burst pattern on the electroencephalography (EEG). The patient showed profound psychomotor developmental delay since early infancy. Daily seizures of versive posturing and ocular deviation were transiently controlled by carbamazepine and valproate at the age of 1 year; however, the seizures gradually increased to up to 50 times per day. Ictal EEG and positron emission tomography revealed an epileptic focus in the left frontal lobe at age 5 years. Total callosotomy resulted in marked reduction of epileptic seizures thereafter, as well as improved responses to external auditory and visual stimuli. Whole exome sequencing at age 9 identified a de novo missense variant in KCNQ2 (NM_172107.3:c.563A > C:p.(Gln188Pro)). CONCLUSION: This case supports that epilepsy surgery could benefit children with epileptic encephalopathy, even with the etiology of channelopathy.

DOI： 10.1016/j.braindev.2020.05.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To elucidate the genetic background and genotype-phenotype correlations for epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy (MAE) or Doose syndrome. METHODS: We collected clinical information and blood samples from 29 patients with MAE. We performed whole-exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. RESULTS: We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic-atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention-deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. SIGNIFICANCE: MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic-atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

DOI： 10.1002/epi4.12417

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Early myoclonic encephalopathy (EME) is a form of developmental and epileptic encephalopathy with myoclonic seizures and a suppression burst on electroencephalogram, which occurs during the neonatal or early infantile period and is characterized by highly intractable seizures and severe development impairment. Although multiple genetic aetiologies of EME have been identified, no SCN1A mutation has been reported. METHODS: We described a female patient with EME due to an SCN1A mutation. RESULTS: She developed frequent myoclonic and apnoeic seizures during the neonatal period. As her seizures were refractory to many antiepileptic drugs, she underwent a tracheotomy and has since been treated with continuous mechanical ventilation. Eventually, perampanel was added, which resulted in the cessation of the apnoeic seizures. Genetic analysis revealed a heterozygous de novo missense mutation in the SCN1A gene (c.2588 T > C:p.Leu863Ser). CONCLUSION: This is the first patient with EME due to anSCN1A mutation to be successfully treated with perampanel. Recently, perampanel was reported to be effective in treating Dravet syndrome, including cases with an SCN1A mutation. Perampanel may contribute to seizure reduction in patients with intractable epilepsy carrying the SCN1A mutation.

DOI： 10.1016/j.seizure.2019.05.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10-6) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.

DOI： 10.1038/s41467-019-10482-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult.

DOI： 10.1111/cga.12269

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記述言語：英語  

Chronic intestinal pseudo-obstruction (CIPO) is a major sign of mitochondrial disorders. We present the first reported case of fetal bowel dilation associated with Leigh syndrome. The possibility of CIPO should be taken into consideration even when mild fetal bowel dilation is detected.

DOI： 10.1002/ccr3.1638

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

症例は31歳女性で、1経妊1経産。妊娠18週に外陰部そう痒感を自覚した。腟分泌物培養検査でCandida albicansが検出され、腟剤の抗真菌薬で治療された。妊娠39週0日、胎動の自覚がなく受診したところ子宮内胎児死亡(IUFD)と診断された。妊娠39週1日、陣痛発来のため入院し、娩出直前に破水し、自然陣痛で経腟分娩に至った。死産児の病理解剖検査を両親の同意を得て行ったところ、肺胞内と気管支内にリンパ球中心の炎症細胞浸潤とカンジダ酵母・仮性菌糸を認め、カンジダ気管支炎および重篤なカンジダ肺炎と診断した。胎盤病理検査で、羊膜と絨毛膜にカンジダ酵母・仮性菌糸を伴うBlancの分類Stage III、急性で重症な絨毛膜羊膜炎を認めた。ただし、絨毛炎は認めなかった。臍帯は動脈、静脈いずれも中山の分類Stage III、急性で重症な炎症が観察された。以上より、IUFDの原因をカンジダ腟炎からの上行性感染による胎児カンジダ感染が関連した可能性を否定できないと考えられた。

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：金原出版(株)  

妊娠・分娩を契機に筋強直性ジストロフィー(DM1)と診断された母体12例について、母児の臨床所見、妊娠分娩経過を後方視的に検討した。母体の臨床所見は無症状～軽微で妊娠中に羊水過多・切迫早産を認め、初めて本症を疑われた症例が多く、症状のない母体DM1の診断は困難であった。胎児所見では羊水過多～羊水増加傾向以外に胎児脳室拡大を高率に認め、新生児は全例先天性筋強直性ジストロフィーでほとんどが34週以降の分娩であったにもかかわらず、重症新生児仮死の割合が高かった。また、DM1患者では塩酸リトドリン投与後の高CK血症を高率に認め、塩酸リトドリン投与中のCKモニタリングは無症状のDM1の早期診断に有用である可能性が示唆された。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J00535&link_issn=&doc_id=20160823130012&doc_link_id=10.18888%2FJ00535.2016357560&url=https%3A%2F%2Fdoi.org%2F10.18888%2FJ00535.2016357560&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)関東連合産科婦人科学会  

原発不明がんの精査で子宮内膜細胞診所見より術前に原発性卵管癌を強く疑い管理した1例を報告する.症例は73歳女性,2回経妊2回経産.左下腿の浮腫を主訴に当院外科を受診した.造影CTで傍大動脈・左外腸骨・左鼠径領域に1.5cmまでのリンパ節腫大を認め,他に明らかな腫瘍性病変は指摘されなかった.原発不明がんの診断・精査目的に当科に併診された.婦人科的診察では,出血や帯下の異常を認めず,3cm大の筋腫のほかに,内膜肥厚,腫瘍性病変や腹水を認めなかった.血液検査ではCA125のみ259.1U/mlと高値であった.子宮腟部細胞診はNILMで,子宮内膜擦過細胞診ではきれいな背景にN/C比の増大した核小体明瞭な異型細胞の集塊を認めた.子宮内膜組織診では異型細胞を認めなかった.卵管癌を念頭に,腹式単純子宮全摘出術,両側付属器摘出術,大網切除術,骨盤リンパ節生検を施行し,術後病理組織診断で左卵管癌IIIc期(漿液性乳頭状腺癌pT3cN1M0)と診断した.明らかな婦人科由来の悪性腫瘍所見が画像や血液検査から同定できず,特に腹水貯留が認められない場合には,子宮内膜細胞診は診断と治療開始の端緒として有用な検査になり得ると考えた.(著者抄録)

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記述言語：日本語   出版者・発行元：神奈川産科婦人科学会  

妊娠性疱疹は妊娠中、産褥期に生じる稀な自己免疫性水疱症である。今回我々は妊娠後期に発症し、中用量プレドニゾロン(以下PSL)療法開始後も増悪を認め、一時的に高用量PSL療法を要し治療した症例を経験したので報告する。症例は28歳、0経妊0経産。妊娠27週頃より皮膚そう痒感が出現し、妊娠28週に四肢に水疱を伴う丘疹を認めた。近医皮膚科で処方されたステロイド外用薬で改善せず、皮疹が全身へと拡大したため妊娠29週に当院皮膚科へ受診した。血液検査所見で本疾患に特徴的な抗BP180抗体が高値を示し、妊娠性疱疹の診断でPSL30mg/dayの内服を開始した。PSL内服後も皮疹の改善はみられず、妊娠30週に入院管理下でPSL60mg/dayへ増量し加療を行った。入院時に施行した皮膚生検で、表皮下水疱と表皮から真皮に浸潤する好酸球を認め、妊娠性疱疹と診断した。PSL増量後、皮疹の改善と抗BP180抗体の低下を認め妊娠31週よりPSLを漸減し、妊娠37週1日骨盤位のため帝王切開分娩で男児を出産したが、周術期に高侵襲レベルとみなしたステロイドカバーを要した。分娩後2ヵ月でPSL5mg/dayまで減量し、現在分娩5ヵ月まで経過したが皮疹の再燃はない。重症化した妊娠性疱疹の治療として妊娠中の高用量PSL投与を行う場合は、副作用に対する適切な情報提供と共に母児への影響を念頭においた慎重な産科管理を行う事が肝要である。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)関東連合産科婦人科学会  

卵巣腫瘍を契機に診断された,びまん性大細胞型B細胞リンパ腫の1例を報告する.症例は73歳女性,2回経妊2回経産.近医より卵巣腫瘍の疑いで当科に紹介された.MRIでは右付属器領域に6cm大,子宮体部に5cm大,大動脈下大静脈前方に5cm大の腫瘤像を認めた.採血ではLDH 524IU/lと高値であった.初診より,1ヵ月の間に急速に腹部膨満感が増強しており,開腹術を施行した.開腹所見では,右卵巣と子宮が8cm大に腫大し,骨盤内・傍大動脈領域のリンパ節は著明に腫大し,一塊の巨大な腫瘤を形成していた.腫瘍生検として右付属器切除を行い,術後病理診断によりびまん性大細胞型B細胞リンパ腫と診断された.Ann Arbor臨床病期分類IV AE,Cotswold分類ではIV AEXであった.術後血液内科へ転科し,オンコビンとエンドキサンによる化学療法を行った.多発する腫瘤像や,LDH高値など通常の卵巣悪性腫瘍と比して非典型的な経過を見た際には悪性リンパ腫の鑑別が必要であると考えられた.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)関東連合産科婦人科学会  

リウマチ性多発筋痛症(Polymyalgia rheumatica以下PMR)は,肩や上腕,大腿などの四肢近位筋の疼痛とこわばり,発熱,倦怠感などを呈する炎症性疾患である.発症は50歳以上が多く,妊娠中を含めた若年者に発症した報告は稀である.今回我々は,妊娠中に発症し,PSL(prednisolone)による加療が著効したPMRの1例を経験したので報告する.症例は24歳,0経妊0経産.妊娠21週より突然四肢末梢に緊満感を自覚した.その後,大腿,上腕の筋痛や筋力低下が急速に進行し,妊娠23週には独歩困難となった.当院神経内科を受診し,炎症反応の上昇と臨床症状よりPMRと診断された.妊娠24週からPSL 15mg/日の内服加療を開始したところ,内服開始4日目より劇的に改善傾向を示し,独歩可能となった.以降,筋痛の消失にしたがい,PSL 10mg/日へ減量し,症状増悪することなく同量投与にて分娩まで維持する方針となった.妊娠39週4日に経腟分娩後は更にPSLを漸減し,分娩約5ヵ月後には離脱した.現在まで再燃を認めていない.PMRが妊孕性のある年代に発症することは稀であるが,PSLの著効が期待できるだけに,血中CK値上昇を伴わない近位筋優位の筋痛を呈した場合には,筋痛症状の変化に注意しつつ,本疾患を念頭においた上で適切に鑑別診断を行いPSLによる加療に繋げることが肝要であると考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J05804&link_issn=&doc_id=20131217120022&doc_link_id=20475&url=http%3A%2F%2Fjsog-k.jp%2Fjournal%2Flfx-journal_detail-id-20475.htm&type=%E9%96%A2%E6%9D%B1%E9%80%A3%E5%90%88%E7%94%A3%E7%A7%91%E5%A9%A6%E4%BA%BA%E7%A7%91%E5%AD%A6%E4%BC%9A%E8%AA%8C%28~%E7%AC%AC51%E5%B7%BB3%E5%8F%B7%29&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00020_3.gif

記述言語：日本語   出版者・発行元：(一社)関東連合産科婦人科学会  

正常大卵巣癌症候群(normal sized ovary carcinoma syndrome,以下NSOCS)は原発不明癌の術前診断として捉えられている概念で,婦人科癌由来であることが多い.今回我々は,胸水貯留を契機とし,術前診断をNSOCSとして治療し得た卵巣原発漿液性腺癌の1例を経験したので報告する.症例は71歳,咳嗽を主訴に近医を受診し,右胸水を指摘.胸水より異型腺細胞を検出するも,血清CA125高値を認め,転移性肺癌を疑われた.CTでは右胸水以外に明らかな異常所見を認めず,腹水も指摘されなかった.PETでは子宮近傍にのみFDG集積を認めたため,婦人科由来の悪性腫瘍を疑われた.子宮内膜吸引細胞診にて子宮外からの異型腺細胞を認め,NSOCSを視野に開腹手術の方針となった.開腹所見より,両側卵巣の腫大がなく,卵巣実質への比較的広範囲の浸潤を認めたこと,病理組織学的に漿液性乳頭状腺癌であったことから原発性卵巣癌IV期と診断した.胸水貯留の機序については,腹膜播種像が広範に認められたことから,直接浸潤による胸膜播種から産生された可能性が考えられた.腹水貯留の明らかでない卵巣癌の術前診断方法として子宮内膜細胞診は有用である.更に,血清CA125値の上昇,PETによる原発巣検索を組み合わせることで,迅速な手術療法を行い得たことが,良好な結果につながったと考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J05804&link_issn=&doc_id=20131217120016&doc_link_id=20469&url=http%3A%2F%2Fjsog-k.jp%2Fjournal%2Flfx-journal_detail-id-20469.htm&type=%E9%96%A2%E6%9D%B1%E9%80%A3%E5%90%88%E7%94%A3%E7%A7%91%E5%A9%A6%E4%BA%BA%E7%A7%91%E5%AD%A6%E4%BC%9A%E8%AA%8C%28~%E7%AC%AC51%E5%B7%BB3%E5%8F%B7%29&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00020_3.gif

記述言語：日本語   出版者・発行元：(株)診断と治療社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00525&link_issn=&doc_id=20130524170014&doc_link_id=%2Fae4sanke%2F2013%2F008006%2F015%2F0777-0783%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2013%2F008006%2F015%2F0777-0783%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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