Abdominal paraganglioma in a young woman with 1p36 deletion syndrome.

1p36 deletion syndrome is the most common terminal deletion syndrome, and the genomic regions that contribute to specific 1p36 deletion syndrome-related phenotypes were recently identified. Deletions in the 1p36 region have been documented in various tumor tissues, which indicates correlation between loss of heterozygosity of 1p36 and tumor development, and the existence of tumor suppressors in this region. Therefore, it was suspected that patients with 1p36 deletion syndrome have a higher risk of tumor development; however, only a few child cases of neuroblastoma with 1p36 deletion syndrome have been reported.

Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis.

A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.

mutations in three Japanese pedigrees with hereditary cavernous malformation.

Cerebral cavernous malformation is a neurovascular abnormality that can cause seizures, focal neurological deficits and intracerebral hemorrhage. Familial forms of this condition are characterized by formation of multiple lesions and are autosomal-dominantly inherited via /, and / mutations. We identified three truncating mutations in from three Japanese families with CCMs: a novel frameshift mutation, a known frameshift mutation and a known splice-site mutation that had not been previously analyzed for aberrant splicing.

Germline mutations in Japanese familial pancreatic cancer patients.

Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC).We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.

Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya Disease.

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins.

Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome.

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by impaired thyroid hormone transporter. Patients with AHDS usually exhibit severe motor developmental delay, delayed myelination of the brain white matter, and elevated T3 levels in thyroid tests. Neurological examination of two patients with neurodevelopmental delay revealed generalized hypotonia, and not paresis, as the main neurological finding.

Mandibulofacial dysostosis with microcephaly: A case presenting with seizures.

We report a case of mandibulofacial dysostosis with microcephaly presenting with seizures. The proband, a 6-year-old Korean boy, had microcephaly, malar and mandibular hypoplasia, and deafness. He showed developmental delay and had suffered recurrent seizures beginning at 21months of age.

A 12p13 GRIN2B deletion is associated with developmental delay and macrocephaly.

N-methyl D-aspartate receptor subtype 2B (GluN2B), encoded by GRIN2B, is one of the components of the N-methyl D-aspartate receptor protein. Aberrations in GRIN2B have been reported to be responsible for various types of neurodevelopmental disorders. We report a Japanese boy with an ~2 Mb interstitial deletion in 12p13 involving the entire GRIN2B gene, who presented with intellectual disability, motor developmental delay and marked macrocephaly.

Inhibition of the integrin signal constitutes a mouse iPS cell niche.

Stem cells are regulated by their surrounding microenvironments, called niche, such as cell-cell interaction and extracellular matrix. Classically, feeder cells as a niche have been used in the culture of iPS cells from both the mouse and the human. However, the regulation mechanism of stem cells by feeder cells as a niche still have been partially unclear.

7p22.1 microdeletions involving ACTB associated with developmental delay, short stature, and microcephaly.

There are no published reports of patients harboring microdeletions involving the 7p22.1 region. Although 7p22.

Challenges in detecting genomic copy number aberrations using next-generation sequencing data and the eXome Hidden Markov Model: a clinical exome-first diagnostic approach.

Next-generation sequencing (NGS) is widely used for the detection of disease-causing nucleotide variants. The challenges associated with detecting copy number variants (CNVs) using NGS analysis have been reported previously. Disease-related exome panels such as Illumina TruSight One are more cost-effective than whole-exome sequencing (WES) because of their selective target regions (~21% of the WES).

Association of Rare Nonsynonymous Variants in PKD1 and PKD2 with Familial Intracranial Aneurysms in a Japanese Population.

Background: Autosomal dominant polycystic kidney disease (ADPKD) caused by deleterious mutations in PKD1 (16p13.3) and PKD2 (4q21) often coexists with intracranial aneurysms (IAs). In this study, we investigated whether IAs without obvious renal diseases were also associated with these ADPKD genes.

A case of Dravet syndrome with cortical myoclonus indicated by jerk-locked back-averaging of electroencephalogram data.

We report a female patient with Dravet syndrome (DS) with erratic segmental myoclonus, the origin of which was first identified in the cerebral cortex by the detection of myoclonus-associated cortical discharges. The discharges were disclosed through jerk-locked back-averaging of electroencephalogram (EEG) data using the muscle activity of myoclonus as triggers. The detected spikes on the contralateral parieto-central region preceded myoclonic muscle activity in the forearms by 28-46ms.

Specific MAPK-Associated MicroRNAs in Serum Differentiate Pancreatic Cancer from Autoimmune Pancreatitis.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to distinguish from autoimmune pancreatitis (AIP) because of their clinical and radiological similarities, and therefore simple and minimally invasive surrogate markers for differential diagnosis would be useful. In our previous studies, we identified four microRNAs (miRNAs)-miR-7, miR-34a, miR-181d, and miR-193b -as MAPK-associated microRNAs whose expression was altered significantly with upregulation of the MAPK signaling pathway. Recently it has been reported that these miRNAs could be used as biomarkers in serum samples for accurate diagnosis of pancreatic lesions.

Intracystic papillary neoplasm with an associated mucinous adenocarcinoma arising in Rokitansky-Aschoff sinus of the gallbladder.

Intraepithelial neoplasias are preinvasive neoplastic lesions found throughout in the digestive system, and when such lesions are discovered in the gallbladder, they are referred to as intracystic papillary neoplasm (ICPN). In the gallbladder, mucinous adenocarcinoma is a rare histologic phenotype, and adenocarcinomas involving Rokitansky-Aschoff (RA) sinuses are uncommon, which were indeed found in a case reported here. A 64-year-old male presenting with upper abdominal pain demonstrated a spherical mass protruding outward from the gallbladder fundus in imaging studies.

Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans.

RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. During systemic spread of RNAi, membrane trafficking is thought to play important roles.

A de novo microdeletion in a patient with inner ear abnormalities suggests that the 10q26.13 region contains the responsible gene.

Microdeletions in the 10q26.1 region are related to intellectual disability, growth delay, microcephaly, distinctive craniofacial features, cardiac defects, genital abnormalities and inner ear abnormalities. The genes responsible for inner ear abnormalities have been narrowed to fibroblast growth factor receptor 2 gene (FGFR2), H6 family homeobox 2 gene (HMX2) and H6 family homeobox 3 gene (HMX3).

A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features.

Interstitial deletions of the 16q centromeric region are rarely reported. A microdeletion of the 16q12.2q21 region was identified in a patient with intellectual disability, epilepsy, short stature, and distinctive features; including up-slanting palpebral fissures, hypertelorism, epicanthic folds, anteverted nares, simple philtrum, thin upper lip vermilion, high arched palate, posteriorly rotated ears, and overlapping toes in his right foot.

Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1.

A de novo microdeletion involving PAFAH1B (LIS1) related to lissencephaly phenotype.

Lissencephaly is a type of the congenital malformation of the brain. Due to the impairments of neuronal migration, patients show absence of brain convolution manifesting smooth brain surfaces. One of the human genes responsible for lissencephaly is the platelet-activating factor acetylhydrolase 1b gene (PAFAH1B; also known as LIS1) located on 17p13.

Tatton-Brown-Rahman syndrome due to 2p23 microdeletion.

Tatton-Brown-Rahman syndrome is a new overgrowth syndrome due to DNMT3A (DNA cytosine 5 methyltransferase 3A) mutations. Mutation carriers show a distinctive facial appearance, intellectual disability, and increased height. We report a patient with overgrowth who showed submicroscopic deletion of chromosome 2p23 including DNMT3A.

A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome.

The p.Asp211Gly homozygous HYLS1 mutation is so far known to cause only hydrolethalus syndrome, a lethal malformation syndrome. We report living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1, NM_145014.