Read by QxMD icon Read


Yoko Shimada, Takashi Kohno, Hideki Ueno, Yoshinori Ino, Hideyuki Hayashi, Takashi Nakaoku, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Kazuaki Shimada, Takuji Okusaka, Nobuyoshi Hiraoka
PURPOSE: Oncogenic mutations in the KRAS gene are a well-known driver event, occurring in >95% of pancreatic cancers. The objective of this study was to identify driver oncogene aberrations in pancreatic cancers without the KRAS mutation. METHODS: Whole-exome and transcriptome sequencing was performed on four cases of KRAS mutation-negative pancreatic ductal adenocarcinoma, which were identified in a cohort of 100 cases. RESULTS: One case harbored an oncogenic DCTN1-ALK fusion...
February 6, 2017: Oncologist
Jen-Chieh Lee, Chien-Feng Li, Hsuan-Ying Huang, Mei-Jun Zhu, Adrián Mariño-Enríquez, Chung-Ta Lee, Wen-Bin Ou, Jason L Hornick, Jonathan A Fletcher
ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case...
February 2017: Journal of Pathology
David E Holt, Dorothy C Brown, Paula S Henthorn
OBJECTIVE To sequence exons and splice consensus sites of the dynactin subunit 1 (DCTN1) gene in Leonbergers and Labrador Retrievers with clinical laryngeal paralysis. ANIMALS 5 unrelated Leonbergers with laryngeal paralysis, 2 clinically normal Leonbergers, 7 unrelated Labrador Retrievers with laryngeal paralysis, and 2 clinically normal Labrador Retrievers. PROCEDURES Primers were designed for the entire coding regions of the DCTN1 gene, a noncoding exon at the 5´ end of the gene, and a 900-bp single-nucleotide polymorphism (SNP)-rich region located 17 kb upstream of the DCTN1 gene by use of the CanFam3 assembly of the canine genome sequence...
October 2016: American Journal of Veterinary Research
Sun Hee Hwang, Eun Ja Kim, Young Bin Hong, Jaesoon Joo, Sung Min Kim, Soo Hyun Nam, Hyun Dae Hong, Seung Hyun Kim, Kiwook Oh, Jeong-Geun Lim, Jeong Hee Cho, Ki Wha Chung, Byung-Ok Choi
Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B (dHMN7B), Perry syndrome, amyotrophic lateral sclerosis and amyotrophic lateral sclerosis‑frontotemporal dementia. However, since the first dHMN7B patient with a DCTN1 mutation was described in 2003, to the best of our knowledge no further cases have been reported. In the present study, the DCTN1 p.G59S mutation was identified in two unrelated families from a total of 24 Korean families with dHMN, by whole exome sequencing...
October 2016: Molecular Medicine Reports
Takayasu Mishima, Taizo Ishikawa, Keiko Imamura, Takayuki Kondo, Yasushi Koshiba, Ryosuke Takahashi, Jun Takahashi, Akihiro Watanabe, Naoki Fujii, Yoshio Tsuboi, Haruhisa Inoue
BACKGROUND: Perry syndrome is a rare autosomal dominant disorder clinically characterized by parkinsonism with depression/apathy, weight loss, and central hypoventilation. Eight mutations in DCTN1 gene have been reported. A novel disease model is required because the detailed pathogenesis remains unclear. METHODS: To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient with F52L mutation in DCTN1, and describe clinical and neuroimaging investigations...
September 2016: Parkinsonism & related Disorders
Emil K Gustavsson, Joanne Trinh, Ilaria Guella, Chelsea Szu-Tu, Jaskaran Khinda, Chin-Hsien Lin, Ruey-Meei Wu, Jon Stoessl, Silke Appel-Cresswell, Martin McKeown, Alex Rajput, Ali H Rajput, Maria Skaalum Petersen, Beom S Jeon, Jan O Aasly, Matthew J Farrer
INTRODUCTION: Mutations in dynactin DCTN1 (p150(glued)) have previously been linked to familial motor neuron disease or Perry syndrome (PS) consisting of depression, parkinsonism and hypoventilation. METHODS: We sequenced DCTN1 in 636 Caucasian patients with parkinsonism (Parkinson's disease and Parkinson-plus syndromes) and 508 healthy controls. Variants (MAF < 0.01) were subsequently genotyped in Caucasian (1360 cases and 1009 controls) and Asian cohorts (1046 cases and 830 controls), and the functional implications of pathogenic variants were assessed...
July 2016: Parkinsonism & related Disorders
Hiroshi Mitsumoto, Peter L Nagy, Chris Gennings, Jennifer Murphy, Howard Andrews, Raymond Goetz, Mary Kay Floeter, Jonathan Hupf, Jessica Singleton, Richard J Barohn, Sharon Nations, Christen Shoesmith, Edward Kasarskis, Pam Factor-Litvak
OBJECTIVE: To understand phenotypic and molecular characteristics of patients with clinically "definite" primary lateral sclerosis (PLS) in a prospective study. METHODS: Six sites enrolled 41 patients who had pure upper motor neuron dysfunction, bulbar symptoms, a normal EMG done within 12 months of enrollment, and onset of symptoms ≥5 years before enrollment. For phenotypic analyses, 27 demographic, clinical, and cognitive variables were analyzed using the k-means clustering method...
June 2015: Neurology. Genetics
Soo Hyun Nam, Young Bin Hong, Young Se Hyun, Da Eun Nam, Geon Kwak, Sun Hee Hwang, Byung-Ok Choi, Ki Wha Chung
Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A...
May 31, 2016: Molecules and Cells
Magdalena Kuźma-Kozakiewicz, Beata Kaźmierczak, Agnieszka Chudy, Beata Gajewska, Anna Barańczyk-Kuźma
BACKGROUND: Sporadic amyotrophic lateral sclerosis (SALS) is a fatal motor neuron degenerative disease of unclear pathogenesis. Disturbances of intracellular transport are possible causes of the disease. OBJECTIVE: We evaluated the expression of motor proteins involved in the anterograde (kinesins KIF1B, KIF5C) and retrograde (KIFC3, dynactin subunits DCTN1 and DCTN3) intracellular transport in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: PBMCs were obtained from 74 SALS patients with different clinical phenotypes, 65 blood donors (healthy control I), and 29 cases with other neurological diseases (disease control II) divided into subgroups IIA (atypical parkinsonism) and IIB (ALS-mimicking disorders)...
2016: Neuro-degenerative Diseases
Jeffrey J Nirschl, Erika L F Holzbaur
Axonal transport is an essential function in neurons, as mutations in either motor proteins or their adaptors cause neurodegeneration. While some mutations cause a complete block in axonal transport, other mutations affect transport more subtly. This is especially true of mutations identified in human patients, many of which impair but do not block motor function in the cell. Dissecting the pathogenic mechanisms of these more subtle mutations requires assays that can tease apart the distinct phases of axonal transport, including transport initiation, sustained/regulated motility, and cargo-specific sorting or delivery...
2016: Methods in Cell Biology
S Tey, A Ahmad-Annuar, A P Drew, N Shahrizaila, G A Nicholson, M L Kennerson
The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported...
August 2016: Clinical Genetics
J Zhang, J Y Huang, Y N Chen, F Yuan, H Zhang, F H Yan, M J Wang, G Wang, M Su, G Lu, Y Huang, H Dai, J Ji, J Zhang, J N Zhang, Y N Jiang, S J Chen, Z G Zhu, Y Y Yu
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis...
2015: Scientific Reports
Vivek Subbiah, Caitlin McMahon, Shreyaskumar Patel, Ralph Zinner, Elvio G Silva, Julia A Elvin, Ishwaria M Subbiah, Chimela Ohaji, Dhakshina Moorthy Ganeshan, Deepa Anand, Charles F Levenback, Jenny Berry, Tim Brennan, Juliann Chmielecki, Zachary R Chalmers, John Mayfield, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Siraj M Ali
BACKGROUND: Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options...
June 11, 2015: Journal of Hematology & Oncology
Daniyal Daud, Helen Griffin, Konstantinos Douroudis, Stephanie Kleinle, Gail Eglon, Angela Pyle, Patrick F Chinnery, Rita Horvath
Whole exome sequencing (WES) is a recently developed technique in genetics research that attempts to identify causative mutations in complex, undiagnosed genetic conditions. Causative mutations are usually identified after filtering the hundreds of variants on WES from an individual's DNA selected by the phenotype. We investigated a patient with a slowly progressive chronic axonal distal motor neuropathy and extrapyramidal syndrome using WES, in whom common genetic mutations had been excluded. Variant filtering identified potentially deleterious mutations in three known disease genes: DCTN1, KIF5A and NEFH, which have been all associated with similar clinical presentations of amyotrophic lateral sclerosis, Parkinsonism and/or hereditary spastic paraplegia...
July 2015: Journal of Neurology
Aglaya G Iyevleva, Grigory A Raskin, Vladislav I Tiurin, Anna P Sokolenko, Natalia V Mitiushkina, Svetlana N Aleksakhina, Aigul R Garifullina, Tatiana N Strelkova, Valery O Merkulov, Alexandr O Ivantsov, Ekatherina Sh Kuligina, Kazimir M Pozharisski, Alexandr V Togo, Evgeny N Imyanitov
Detection of ALK rearrangements in patients with non-small cell lung cancer (NSCLC) presents a significant technical challenge due to the existence of multiple translocation partners and break-points. To improve the performance of PCR-based tests, we utilized the combination of 2 assays, i.e. the variant-specific PCR for the 5 most common ALK rearrangements and the test for unbalanced 5'/3'-end ALK expression. Overall, convincing evidence for the presence of ALK translocation was obtained for 34/400 (8.5%) cases, including 14 EML4ex13/ALKex20, 12 EML4ex6/ALKex20, 3 EML4ex18/ALKex20, 2 EML4ex20/ALKex20 variants and 3 tumors with novel translocation partners...
June 28, 2015: Cancer Letters
John C Steele, Ilaria Guella, Chelsea Szu-Tu, Michelle K Lin, Christina Thompson, Daniel M Evans, Holly E Sherman, Carles Vilariño-Güell, Katrina Gwinn, Huw Morris, Dennis W Dickson, Matthew J Farrer
OBJECTIVE: Amyotrophic lateral sclerosis/parkinsonism-dementia complex has been described in Guam, Western Papua, and the Kii Peninsula of Japan. The etiology and pathogenesis of this complex neurodegenerative disease remains enigmatic. METHODS: In this study, we have used targeted genomic sequencing to evaluate the contribution of genetic variability in the pathogenesis of amyotrophic lateral sclerosis, parkinsonism, and dementia in Guamanian Chamorros. RESULTS: Genes previously linked to or associated with amyotrophic lateral sclerosis, parkinsonism, dementia, and related neurodegenerative syndromes were sequenced in Chamorro subjects living in the Mariana Islands...
March 2015: Annals of Neurology
Shin Kedashiro, Strahil Iv Pastuhov, Tomoki Nishioka, Takashi Watanabe, Kozo Kaibuchi, Kunihiro Matsumoto, Hiroshi Hanafusa
The binding of ligand to epidermal growth factor receptor (EGFR) causes the receptor to become activated and stimulates the endocytosis of EGFR. Early endosomes containing activated EGFR migrate along microtubules as they mature into late endosomes. We have recently shown that LRRK1, which is related to the familial Parkinsonism gene product Park8 (also known as LRRK2), regulates this EGFR transport in a manner dependent on LRRK1 kinase activity. However, the downstream targets of LRRK1 that might modulate this transport function have not been identified...
January 15, 2015: Journal of Cell Science
Zhi-Jun Liu, Hong-Fu Li, Guo-He Tan, Qing-Qing Tao, Wang Ni, Xue-Wen Cheng, Zhi-Qi Xiong, Zhi-Ying Wu
To date, at least 18 causative genes have been identified in amyotrophic lateral sclerosis (ALS). Because of the clinical and genetic heterogeneity, molecular diagnosis for ALS faces great challenges. HaloPlex target enrichment system is a new targeted sequencing approach, which can detect already known mutations or candidate genes. We performed this approach to screen 18 causative genes of ALS, including SOD1, SETX, FUS, ANG, TARDBP, ALS2, FIG4, VAPB, OPTN, DAO, VCP, UBQLN2, SPG11, SIGMAR1, DCTN1, SQSTM1, PFN1, and CHMP2B in 8 ALS probands...
December 2014: Neurobiology of Aging
Pawel Tacik, Fabienne C Fiesel, Shinsuke Fujioka, Owen A Ross, Felipe Pretelt, Camilo Castañeda Cardona, Alexa Kidd, Michael Hlavac, Anthony Raizis, Michael S Okun, Sharleen Traynor, Audrey J Strongosky, Wolfdieter Springer, Zbigniew K Wszolek
OBJECTIVES: Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1. METHODS: Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency...
August 2014: Parkinsonism & related Disorders
Andre C Felicio, Katherine Dinelle, Pankaj A Agarwal, Jessamyn McKenzie, Nicole Heffernan, Jeremy D Road, Silke Appel-Cresswell, Zbigniew K Wszolek, Matthew J Farrer, Michael Schulzer, Vesna Sossi, A Jon Stoessl
INTRODUCTION: We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. METHODS: All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter)...
August 2014: Movement Disorders: Official Journal of the Movement Disorder Society
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"