Somatic mosaic deletions involving SCN1A cause Dravet syndrome.

Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a subset of parents of children with Dravet syndrome (DS). Here, we report recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed with DS. Through the evaluation of 237 affected individuals with DS who did not show SCN1A or PCHD19 mutations in prior sequencing analyzes, we identified two children with mosaic microdeletions covering the entire SCN1A region.

A case of long-survival insulinoma with multiple neuroendocline tumour type 1 controlled by multimodal therapy.

Insulinomas with multiple neuroendocrine tumour type 1 (MEN1) sometimes have metachronous or recurrent tumours. However, the treatment for these tumours is controversial, and published reports regarding multimodal therapy for insulinomas are limited. We report a 73-year-old woman with recurrent insulinoma with MEN1 successfully controlled by multimodal therapy.

The smallest 20q11.2 microdeletion causing intellectual disability and dysmorphic features.

The 20q11.2 microdeletion is a rare chromosomal aberration characterized by intellectual disability (ID), motor developmental delay, neonatal feeding problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl with a 1.

Multicenter study of early pancreatic cancer in Japan.

Background/objectives: The diagnosis of early-stage pancreatic ductal adenocarcinoma (PDAC) is still challenging. We conducted a multicenter study to clarify the clinical features of early-stage PDAC in Japan.

Methods: We collected patients with stage 0 and stage I PDAC according to the sixth edition of the Japanese Classification of Pancreatic Carcinoma.

Comprehensive functional genomics using Caenorhabditis elegans as a model organism.

We have been working on functional genomics using C. elegans as a model organism. We first used cell-type specific markers and preexisting mutants to investigate how genotype-phenotype causal relationships are regulated.

Characteristics of rare and private deletions identified in phenotypically normal individuals.

Genomic copy number variations (CNVs) identified through chromosomal microarray testing must be validated to confirm whether they are pathogenically and functionally relevant to their respective clinical features. Although larger deletions have a higher probability to be pathogenic, this is not always true. Phenotypically normal individuals showed five CNV deletions larger than 1.

A long-term recurrence-free survival of a patient with the mixed adeno-neuroendocrine bile duct carcinoma: A case report and review of the literature.

Introduction: Neuroendocrine tumors arising primarily in the bile duct are rare. And among these tumors, mixed adeno-neuroendocrine carcinoma (MANEC) is quite uncommon. We report a patient with MANEC who achieved long-term recurrence-free survival.

Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma.

Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized.

ENBD is Associated with Decreased Tumor Dissemination Compared to PTBD in Perihilar Cholangiocarcinoma.

Background: Little is known regarding the risk of tumor dissemination when percutaneous biliary drainage is used before surgical resection of perihilar cholangiocarcinoma (PHC). We aimed to compare the incidence of tumor dissemination after preoperative endoscopic nasobiliary drainage (ENBD) with that after percutaneous transhepatic biliary drainage (PTBD) for PHC.

Methods: Data from 208 consecutive patients who underwent PHC resection between 2000 and 2013 were retrospectively analyzed.

Relationship between pancreatic intraepithelial neoplasias, pancreatic ductal adenocarcinomas, and single nucleotide polymorphisms in autopsied elderly patients.

We comparatively analyzed serially autopsied, elderly Japanese patients (n = 2205) with pancreatic intraepithelial neoplasias (PanINs) and pancreatic ductal adenocarcinomas (PDACs) on the basis of their pancreatic lesions, clinical information, and single nucleotide polymorphisms (SNPs). The incidence of PanIN-1, -2, -3, and PDACs in these patients was 55%, 12%, 1.4%, and 2.

High-grade dysplasia/carcinoma in situ of the bile duct margin in patients with surgically resected node-negative perihilar cholangiocarcinoma is associated with poor survival: a retrospective study.

Background: The clinical relevance of a high-grade dysplasia/carcinoma in situ (HD/CIS)-positive bile duct margin in perihilar cholangiocarcinoma (PHC) is unclear. We evaluated the surgical outcomes of PHC patients with HD/CIS.

Methods: Clinicopathological data of 163 consecutive patients who underwent resection of PHC between 2004 and 2013 were analyzed retrospectively.

A Video Report of Brain-Lung-Thyroid Syndrome in a Japanese Female With a Novel Frameshift Mutation of the Gene.

Benign hereditary chorea is a rare autosomal-dominant disorder that is characterized by childhood-onset nonprogressive chorea and normal cognitive function. Defects in on chromosome 14q13, which encodes thyroid transcription factor 1, produce a concurrent clinical manifestation of chorea, respiratory distress, and hypothyroidism known as "brain-lung-thyroid syndrome." Here, the authors describe a video report of benign hereditary chorea in a Japanese female with a novel frameshift mutation of (c.

GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in .

Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified as a novel regulator of apoptotic cell clearance in Loss of affects phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of the GOP-1 transiently associates with cell corpse-containing phagosomes, and loss of its function abrogates phagosomal association of UNC-108.

An Xq22.1q22.2 nullisomy in a male patient with severe neurological impairment.

The proteolipid protein 1 gene (PLP1) is located on chromosome Xq22.2 and is related to X-linked recessive leukoencephalopathy (Pelizaeus-Merzbacher disease: PMD). Compared to PLP1 duplications, which are a major contributor to PMD, chromosomal deletions in this region are rare and only a few PMD patients with small deletions have been reported, suggesting that large deletions of this region would cause embryonic lethality.

A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

Background: Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer.

Methods: We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014.

The Prevalence and Clinicopathological Characteristics of High-Grade Pancreatic Intraepithelial Neoplasia: Autopsy Study Evaluating the Entire Pancreatic Parenchyma.

Objective: We sought to identify clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia (PanIN)/carcinoma in situ to facilitate screening for pancreatic ductal adenocarcinoma.

Methods: We evaluated PanIN lesions in 173 consecutive autopsy cases with no evidence of pancreatic ductal adenocarcinoma and/or intraductal papillary mucinous neoplasm (mean age, 80.5 years) by submitting the entire pancreas for microscopic examination.

Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan.

Background: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging.

Possible genes responsible for developmental delay observed in patients with rare 2q23q24 microdeletion syndrome: Literature review and description of an additional patient.

Cases of 2q23q24 microdeletion syndrome are rare. Patients with chromosomal deletions in this region often show language impairment and/or developmental delay of variable severity. Previous genotype-phenotype correlation study suggested GALNT13 and KCNJ3 as possible candidate genes for such phenotypes.

Prognostic predictive value of gene mutations in Japanese patients with hypertrophic cardiomyopathy.

Although some studies have attempted to find useful prognostic factors in hypertrophic cardiomyopathy (HCM), those results are not fully helpful for use in actual clinical practice. Furthermore, several genetic abnormalities associated with HCM have been identified. However, the genotype-phenotype correlation in HCM remains to be elucidated.

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms.

The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations.

Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.