Yo Niida

• Kanazawa Medical University

RNA sequencing (RNA-Seq) is a powerful technique for the quantification of transcripts and the analysis of alternative splicing. Previously, our laboratory developed the targeted RNA long-amplicon sequencing (rLAS) method, which has the advantage of allowing deep analysis of targeted specific transcripts. The computational tools for analyzing RNA-S...

DNA methylation of tumor suppressor genes in cancer is known to be a mechanism for silencing gene expression, but much remains unknown about its extent and relationship to somatic variants at the DNA sequence level. In this study, we comprehensively analyzed DNA methylation and somatic variants of all gene regions across the genome of the major tum...

DNA methylation of tumor suppressor genes in cancer is known to be a mechanism for silencing gene expression, but much remains unknown about its extent, degree, and rela-tionship to somatic variants at the DNA sequence level. In this study, we comprehensively analyzed DNA methylation and somatic variants of all gene regions across the genome of the...

Key Clinical Message CYP3A4 and CYP3A5 are the most abundant and important enzymes of the CYP3A subfamily, distributed in the liver, intestinal mucosa and kidney, and involved in tacrolimus metabolism. Here, we report a case of tacrolimus dosage refractoriness due to a genetic polymorphism of CYP3A5.

Here, we report a novel PROS1 splicing mutation in a patient with type I protein S deficiency. Qualitative and quantitative analysis of pathogenic splicing variants at the mRNA level was performed by long-range PCR-based targeted DNA and RNA sequencing. A base substitution in the exon 4 splicing donor site activates a potential splicing donor site...

RNA sequencing (RNA-Seq) is a powerful technique and is increasingly being used in clinical research and drug development. Currently, several RNA-Seq methods have been developed. However, the relative advantage of each method for degraded RNA and low-input RNA, such as RNA samples collected in the field of clinical setting, has remained unknown. Th...

The phenotypes associated with MED12 pathogenic variants are diverse. Male patients usually have missense variants, but the effects of base substitutions on mRNA splicing have not been investigated. Here, we report a Japanese brother with intellectual disability, characteristic facial appearance with blepharophimosis, cleft palate, Fallot tetralogy...

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay...

In the practice of clinical genetics, gene testing is usually guided by clinical diagnosis. When dealing with rare diseases, it is often necessary to create new test systems. The handling of a gene with a substantial number of exons poses a challenge both in sequential Sanger sequencing for each exon, and in the setup of capture probes to each exon...

Recessive dystrophic epidermolysis bullosa is a genetic collagen disorder characterized by skin fragility that leads to generalized severe blistering, wounds, and scarring. In this report, we present a patient with a novel COL7A1 homozygous nonsense variant, c.793C>T p.(Gln265*). Although the parents were not consanguineous, both were heterozygous...

Advances in genetic technologies have made genetic testing more accessible than ever before. However, depending on national, regional, legal, and health insurance circumstances, testing procedures may still need to be streamlined in real-world clinical practice. In cases of autosomal recessive disease with consanguinity, the mutation locus is neces...

Dendritic cells (DCs) are the most potent antigen-presenting cells, playing an essential role in the pathogen and tumor recognition, and anti-tumor immunity, and linking both the innate and adaptive immunity. The monocyte-derived DCs generated by ex vivo culture, have been used for cancer immunotherapy to eliminate tumor; however, the clinical effi...

Tuberous sclerosis complex (TSC) is a relatively common autosomal dominant disorder characterized by multiple dysplastic organ lesions and neuropsychiatric symptoms caused by loss-of-function mutation of either TSC1 or TSC2. The genetic diagnosis of inherited diseases, including TSC, in the clinical field is widespread using next-generation sequenc...

Background Since 2019, cancer genome panel testing in Japan has been covered under healthcare insurance. However, the usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains insufficiently explored. Therefore, herein, we conducted a large-scale study to determine the usefulness of CGP in digestive can...

Simple Summary In this study, we developed human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes with a high potency of presentation ability. This study aimed to verify the safety, tolerability, and immunoinducibility of HPL-APCs loaded with cancer candidate antigens as a Phase I study. As a result of the inter...

New clinical issues have been raised through an interval of 7 years from the previous version (2016). In this study, we update the "Clinical Practice Guidelines for tuberous sclerosis complex-associated renal angiomyolipoma" as a 2023 version under guidance by the Japanese Urological Association. The present guidelines were cooperatively prepared b...

Schimmelpenning-Feuerstein-Mims syndrome (SFMS), an epidermal nevus disease, features skin lesions including craniofacial nevus sebaceous and extracutaneous anomalies (e.g. brain, eye, and bone). Recent genetic studies implicate HRAS, KRAS, and NRAS genes in somatic mutations. Our case, a 48-year-old man, presented with nevus sebaceous on the scalp...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by neuropsychiatric symptoms and multiple dysplastic organ lesions, caused by loss of function mutations in either TSC1 or TSC2. The peripheral blood mononuclear cells (PBMCs) from a patient carrying mosaic nonsense mutation of TSC2 gene were reprogrammed using the Cyt...

Interactions between cancer cells and glial cells play a crucial role in the formation of brain metastases; however, there are few methods to stably analyse these events in vitro over a long period of time. Here, we develop a simple and stable culture method, termed mixed-glial culture on/in soft substrate (MGS), which favourably mimics the brain m...

Prolidase deficiency (PD) is a rare autosomal recessive disorder characterized mainly by skin lesions of the legs and feet, respiratory infections and mental retardation, and impaired immune system. To date, no effective PD treatment has been developed. The PD case are caused by homozygous mutation in PEPD gene. The peripheral blood mononuclear cel...

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8⁺ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeti...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multiple dysplastic organ lesions and neuropsychiatric symptoms, caused by loss of function mutations in either TSC1 or TSC2. Genotype and phenotype analyses are conducted worldwide, but there have been few large-scale studies on Japanese patients, and there are sti...

Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human beta papillomaviruses and a high rate of progression to squamous cell carcinoma on sun-exposed skin. The majority of EV cases are caused by homozygous mutation in TMC8. The peripheral blood mononuclear cells from a patient car...

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomalies syndrome caused by mutations in the cohesion complex. The mutations in NIPBL, one of cohesion regulatory proteins, are the most frequent cause of CdLS. The peripheral blood mononuclear cells (PBMCs) from a patient carrying a heterozygous 3bp deletion in Exon 37 of the NIPBL gene w...

Familial adenomatous polyposis (FAP) is a disorder characterized by the development of numerous colorectal adenomatous polyps progressing to colorectal cancers and has been used as an important model to study the neoplasia formation. The peripheral blood mononuclear cells from a patient carrying a heterozygous 1bp deletion in Exon 17 of the APC gen...

The full-length double-strand cDNA sequencing, one of the RNA-Seq methods, is a powerful method used to investigate the transcriptome status of a gene of interest, such as its transcription level and alternative splicing variants. Furthermore, full-length double-strand cDNA sequencing has the advantage that it can create a library from a small amou...

A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonar...

Background mRNA sequencing is a powerful technique, which is used to investigate the transcriptome status of a gene of interest, such as its transcription level and splicing variants. Presently, several RNA sequencing (RNA-Seq) methods have been developed; however, the relative advantage of each method has remained unknown. Here we used three comme...

Telangiectasia, hereditary hemorrhagic, type 2 (HHT2) is a rare autosomal dominant disease caused by a mutated ACVRL1 gene (Letteboer et al., 2005). The peripheral blood mononuclear cells (PBMCs) from a patient carrying a heterozygous 2bp duplication in intron 6 of the ACVRL1 gene, NG_009549.1(NM_000020.2):c.772+3_772+4dup, were reprogrammed using...

PurposeSubependymal giant cell astrocytomas (SEGAs) are tumors that usually arise in the wall of one or the other lateral ventricle near a foramen of Monro, most often on a background of tuberous sclerosis complex (TSC). TSC has a variety of clinical manifestations caused by germline mutations of the TSC complex subunit 1 or 2 (TSC1, TSC2) genes. S...

Human hereditary malformation syndromes are caused by mutations in the genes of the signal transduction molecules involved in fetal development. Among them, the Sonic hedgehog (SHH) signaling pathway is the most important, and many syndromes result from its disruption. In this review, we summarize the molecular mechanisms and role in embryonic morp...

Background mRNA sequencing is a powerful technique, which is used to investigate the transcriptome status of a gene of interest, such as its transcription level and splicing variants. Presently, several RNA sequencing (RNA-Seq) methods have been developed; however, the relative advantage of each method has remained unknown. Here we used three comme...

A woman with a diagnosis of tuberous sclerosis complex (TSC) presented with TSC2 gene mutation and various manifestations, including epilepsy, renal angiomyolipomas (AML), and pathologically confirmed multifocal micronodular pneumocyte hyperplasia (MMPH). With oral administration of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, MMPH...

Perilipin-2, a lipid droplet (LD) coating protein, has been found to be involved in cancer progression. However, its role in hepatoblastoma (HB) is undefined. We collected 87 HB samples and the corresponding clinical data. Immunohistochemistry (IHC) staining was performed to detect perilipin-2 and the association of the perilipin-2 expression with...

Elaborate analyses of the status of gene mutations in neurofibromatosis type 1 (NF1) are still difficult nowadays due to the large gene sizes, broad mutation spectrum, and the various effects of mutations on mRNA splicing. These problems cannot be solved simply by sequencing the entire coding region using next-generation sequencing (NGS). We recent...

Aim: Dravet syndrome (DS) is characterized by high epilepsy-related premature mortality with a markedly young age at death, however, autopsy report of sudden unexpected death with DS has been fewer than expected. Methods: We report two autopsy cases with sudden unexpected death from DS. Case 1 was a 13-year-old male who drowned in a bathtub, and...

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a rare pulmonary disease, generally manifesting as a tuberous sclerosis complex (TSC), characterised by multiple, small ground-glass nodular shadows on chest computed tomography (CT). Histological examination typically reveals multicentric, well-demarcated, nodular type II pneumocystic growth...

Immunohistochemical staining of normal lung specimens in patient 2. Non-multifocal micronodular pneumocyte hyperplasia (MMPH) parts of lung in patient 2 were assessed immunohistochemically. High-power views (x200). Phospho-p70S6K positive parts (A) and negative parts (B) were observed. Likewise for phospho-4E-BP1, there were positive parts (C) and...

Full-length agarose gel electrophoresis of reverse transcription-polymerase chain reaction (RT-PCR) products corresponding to Fig 4A. Lane 2 is the negative control. Molecular grade water was used instead of template DNA. In lanes 3 and 4, the template DNA used in lane 1 was diluted to one-third of the original concentration. Lanes 5 and 6 do not c...

Next-generation sequencing for 160 cancer-related genes including TSC1 and TSC2. (XLSX)

Full-length agarose gel electrophoresis of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) products corresponding to Fig 5C. Lane 8 contains half of the DNA used in lane 2 treated with half of the restriction enzyme compared to lanes 1 through 5. Lanes 6, 7, 9, and 10 did not contain a DNA sample. (TIF)

CEL nuclease-mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining (CHIPS) analysis and long-range polymerase chain reaction (PCR) analysis for TSC1 and TSC2. (XLS)

Full-length agarose gel electrophoresis of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) products corresponding to Fig 5B. The portion surrounded by the white square frame was inverted horizontally and used in Fig 5B, which shows the PCR-RFLP for patient 2. Lane numbers coincide with those in Fig 5B. The samples from...

Loss of heterozygosity (LOH) analysis of lung tissue from patient 1 (daughter). Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) revealed that mutant alleles increased due to LOH in all lung lesions of patient 1 (daughter). (A) DNA was extracted from four lesions in paraffin-embedded lung tissue obtained via video...

Densitometry analysis of lung lesions of Patient 1 (daughter). (DOCX)

I-cell disease is characterized by the presence of vacuole-like inclusions in lymphocytes. However, the nature and clinical significance of these inclusions have seldom been characterized. In this study, the authors tried to elucidate the distribution in different lymphocyte subpopulations, and the histological nature of the inclusions. Blood sampl...

Patients with autosomal recessive (AR) disorders are usually born to parents both of whom are heterozygous carriers of the disease. However, in some instances only one of the parents is a carrier and a mutation is segregated to the patient through uniparental isodisomy (UPiD). Recently, an increasing number of such case reports has been published,...

GLI family zinc finger proteins are transcriptional effectors of the sonic hedgehog signaling pathway. GLI regulates gene expression and repression at various phases of embryonic morphogenesis. In humans, 4 GLI genes are known, and GLI2 (2q14.2) and GLI3 (7p14.1) mutations cause different syndromes. Here, we present 2 distinctive cases with a chrom...

Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Mul...

The Say–Barber–Biesecker–Young–Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation. Genotype–phenotype correlation is assumed, but a few patients manifest overlapping features of both syndromes. Here we report the case of a boy with SBBYSS. He had a KAT...

Background: Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disorder starting in infancy as early as 12-month-old, caused by PPT1 (palmitoyl-protein thioesterase 1) mutations, and characterized by progressive psychomotor deterioration, brain atrophy, myoclonic jerk and visual impairment. INCL can be diagnosed by brain mag...

Approximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly r...

No abstract is available for this article.

Muir-Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We repor...

Mutation analysis of NF1, the responsible gene for neurofibromatosis type 1 (NF1), is still difficult due to its large size, lack of mutational hotspots, the presence of many pseudogenes, and its wide spectrum of mutations. To develop a simple and inexpensive NF1 genetic testing for clinical use, we analyzed five Japanese families with NF1 as a pil...

In current practice of clinical genetics, molecular diagnosis has become more widely used than ever before. DNA diagnosis is important for appropriate medical care of the patient, and proper genetic counseling to the family. However, genetic testing of orphan disease cannot always be performed easily. In multiple congenital anomalies (MCA) syndrome...

X-linked thrombocytopenia (XLT) is caused by mutations in the WAS gene and characterized by thrombocytopenia with minimal or no immunodeficiency. Patients with XLT usually exhibit persistent thrombocytopenia, and intermittent thrombocytopenia has been described only in two families. Here, we report a patient with intermittent XLT carrying a novel m...

To examine the risk factors of hypocarnitinemia and hypocarnitinemic symptoms in children and adults with severe physical and mental disabilities. The status of hypocarnitinemia as well as the related symptoms were assessed in a total of 78 children and adults with severe physical and mental disabilities who were admitted to National Hospital Organ...

Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG...

Alagille syndrome (AGS) is an autosomal-dominant multi-organ disorder involving the liver, heart, eyes, face and skeleton. In addition, various renal abnormalities have also been reported in several cases. We describe a patient with a novel frameshift mutation in exon 12 of the JAG1 gene who presented with chronic renal failure. In this family, fiv...

Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described....

Socio-communicative impairments are salient features of autism spectrum disorder (ASD) from a young age. The anterior prefrontal cortex (aPFC), or Brodmann area 10, is a key processing area for social function, and atypical development of this area is thought to play a role in the social deficits in ASD. It is important to understand these brain fu...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multiple hamartias and hamartomas involving throughout the body. To date, many TSC1 and TSC2 mutations have been reported all over the world, however, few TSC mutation studies have been performed in the Japanese population, and genetic characteristics of Japanese TS...

A subset of individuals with autism spectrum disorder (ASD) performs more proficiently on certain visual tasks than may be predicted by their general cognitive performances. However, in younger children with ASD (aged 5 to 7), preserved ability in these tasks and the neurophysiological correlates of their ability are not well documented. In the pre...

Establishing a simple and effective mutation screening method is one of the most compelling problems with applying genetic diagnosis to clinical use. Because there is no reliable and inexpensive screening system, amplifying by PCR and performing direct sequencing of every coding exon is the gold standard strategy even today. However, this approach...

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency of the enzyme arylsulfatase A encoded by the ARSA gene located on 22q13.33. Typically, in autosomal recessive disease, a patient inherits two mutations from both parents who are heterozygous carriers. However, in some instances, it is possibl...

Increasing evidence suggests imprinted genes influence mouse and human behaviors and cognitive functions. Unlike autosomal imprinted genes, X-linked imprinted genes are expressed in a sex-dependent manner because of male hemizygosity. Therefore, these genes could directly affect sex-specific brain functions and sex-biased vulnerability to psychiatr...

2176 Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy by exposing isolated white blood cells to photoactive 8-MOP (psoralen) and UVA radiation (PUVA) for refractory acute and chronic graft-versus-host disease (GVHD). Although the effects of PUVA treatment on immune system remain poorly characterized, we have repo...

ejd.2011.1542 Auteur(s) : Yukari Yoshimura1, Chihiro Nishijima1, Kazuo Ikeda2, Keiko Ikeda3, Yo Niida4, Makoto Inaoki1 inaoki-m@kinbyou.hosp.go.jp 1 Department of Dermatology 2 Department of Orthopedic Surgery 3 Department of Cardiology, National Hospital Organization Kanazawa, Medical Center, Kanazawa, 1-1 Shimoishibiki-machi, Ishikawa 920-8650, J...

We report on a 9-year-old boy who presented with acute encephalopathy and hemophagocytic lymphohistiocytosis (HLH). The patient was referred to our hospital because of fever, seizures, and decreased consciousness. He showed moderately elevated levels of proinflammatory cytokines in the cerebrospinal fluid and plasma, and clonal expansion of highly...

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant dermatosis, and characterized by multiple lung cysts, spontaneous pneumothorax, and renal tumors. A 39-year-old woman visited our hospital because of left spontaneous pneumothorax. She had a previous history of surgery for right sided pneumothorax. Chest CT scan showed multiple cystic changes o...

Th17 is a newly identified T cell lineage that secretes the proinflamatory cytokine IL-17. Th17 cells have been shown to play a crucial role in mediating autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), arthritis, and colitis. However, recent study showed that donor Th17 cell ameliorated acute graft-versus-host disease (...

Efficient screening of unknown DNA variations is one of the substantive matters of molecular biology even today. Historically, SSCP and heteroduplex analysis (HA) are the most commonly used methods for detecting DNA variations everywhere in the world because of their simplicity. However, the sensitivity of these methods is not satisfactory for scre...

To report successful management of acute stage toxic epidermal necrolysis (TEN) by amniotic membrane transplantation. Interventional case report. METHOD/INTERVENTION: A 6-year-old boy who had convulsions and fever due to encephalitis was treated by oral phenobarbital. Two weeks later, he developed a high fever and skin rashes involving >40% of the...

The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. The neurofibromatosis 2 (NF2) locus is inactivated in 50-60% of sporadic meningiomas, but the genetic basis of sporadic meningiomas not inactivated at the NF2 locus remains unclear. Specifically, there is conflicting data regarding the role of the tum...