Read by QxMD icon Read


Helen Ross-Adams, Stephen Ball, Kate Lawrenson, Silvia Halim, Roslin Russell, Claire Wells, Siri H Strand, Torben F Ørntoft, Melissa Larson, Sebastian Armasu, Charles E Massie, Mohammad Asim, Martin M Mortensen, Michael Borre, Kathryn Woodfine, Anne Y Warren, Alastair D Lamb, Jonathan Kay, Hayley Whitaker, Antonio Ramos-Montoya, Adele Murrell, Karina D Sørensen, Brooke L Fridley, Ellen L Goode, Simon A Gayther, John Masters, David E Neal, Ian G Mills
Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues...
October 9, 2016: Oncotarget
R El-Khairi, L Vallier
Heterozygous mutations in the gene that encodes the transcription factor hepatocyte nuclear factor 1β (HNF1B) result in a multi-system disorder. HNF1B was initially discovered as a monogenic diabetes gene; however, renal cysts are the most frequently detected feature. Other clinical features include pancreatic hypoplasia and exocrine insufficiency, genital tract malformations, abnormal liver function, cholestasis and early-onset gout. Heterozygous mutations and complete gene deletions in HNF1B each account for approximately 50% of all cases of HNF1B-associated disease and may show autosomal dominant inheritance or arise spontaneously...
September 2016: Diabetes, Obesity & Metabolism
L G Kondratyeva, A A Sveshnikova, E V Grankina, I P Chernov, M R Kopantseva, E P Kopantzev, E D Sverdlov
We show characteristic morphological changes corresponding to epithelial-mesenchymal transition (EMT) program fulfillment in PANC1 cell line stimulated with TGFβ1. Our results support downregulation of E-cadherin protein. We show 5- and 28-fold increase in SNAI1 and SNAI2 expression levels and 25- and 15-fold decrease in CDH1 and KRT8 expression levels, respectively, which confirms the EMT-program fulfillment. We demonstrate downregulation of expression of pancreatic master genes SOX9, FOXA2, and GATA4 (2-, 5-, and 4-fold, respectively) and absence of significant changes in HES1, NR5A2, and GATA6 expression levels in the cells stimulated with TGFβ1...
July 2016: Doklady. Biochemistry and Biophysics
Naoko Iwasaki, Masashi Tsurumi, Kuniya Asai, Wataru Shimuzu, Atsushi Watanabe, Makiko Ogata, Miho Takizawa, Risa Ide, Toshiyuki Yamamoto, Kayoko Saito
The hepatocyte nuclear factor 1β gene (HNF1B) is responsible for maturity-onset diabetes of the young type 5 (MODY5), which is characterized by early-onset diabetes mellitus and urogenital malformations. HNF1B is expressed during visceral endoderm formation. We identified a disruption of the great pancreatic artery in a patient with MODY5 with no pancreatic body or tail. Our finding supports the significance of HNF1B in the development of the pancreas.
2016: Human Genome Variation
Rafael Ríos-Tamayo, Carmen Belén Lupiañez, Daniele Campa, Thomas Hielscher, Niels Weinhold, Joaquin Martínez-López, Andrés Jerez, Stefano Landi, Krzysztof Jamroziak, Charles Dumontet, Marzena Wątek, Fabienne Lesueur, Rui Manuel Reis, Herlander Marques, Artur Jurczyszyn, Ulla Vogel, Gabriele Buda, Ramón García-Sanz, Enrico Orciuolo, Mario Petrini, Annette J Vangsted, Federica Gemignani, Asta Försti, Hartmut Goldschmidt, Kari Hemminki, Federico Canzian, Manuel Jurado, Juan Sainz
Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg...
July 18, 2016: Oncotarget
Maria Rasmussen, Else Marie Vestergaard, Jesper Graakjaer, Yanko Petkov, Iben Bache, Christina Fagerberg, Maria Kibaek, Dea Svaneby, Olav Bjørn Petersen, Charlotte Brasch-Andersen, Lone Sunde
17q12 deletions and duplications are two distinct, recurrent chromosomal aberrations usually diagnosed by chromosomal microarray analysis (CMA). The aberrations encompass the genes, HNF1B, LHX1, and ACACA, among others. We here describe a large national cohort of 12 phenotyped patients with 17q12 deletions and 26 phenotyped patients with 17q12 duplications. The total cohort includes 19 index patients and 19 family members. We also reviewed the literature in order to further improve the basis for the counseling...
July 13, 2016: American Journal of Medical Genetics. Part A
H Heuvel-Borsboom, H W de Valk, M Losekoot, J Westerink
Maturity onset diabetes of the young (MODY) is a monogenic, autosomal dominant form of diabetes characterised by mutations in genes resulting in dysfunction of pancreatic β-cells and subsequent insulin production. We present a family with HNF1A-MODY due to a likely pathogenic mutation in HNF1A (c.59G>A, p.Gly20Glu), diagnosed a long time after the first diagnosis of diabetes. Currently 13 MODY subtypes caused by mutations in 13 genes, are known. We describe the four most prevalent forms in more detail, i...
June 2016: Netherlands Journal of Medicine
Renata P Dotto, Fernando M A Giuffrida, Luciana Franco, Andreia L G Mathez, Leticia S Weinert, Sandra P Silveiro, Joao R Sa, Andre F Reis, Magnus R Dias-da-Silva
Thirty-two patients with diabetes negative for point mutations in GCK and HNF1A underwent further molecular screening of GCK, HNF1A, HNF4A, and HNF1B by MLPA analysis. We described the first Brazilian case of MODY5 due to a heterozygous whole-gene deletion in HNF1B, who developed rapidly progressive renal failure and death.
June 2016: Diabetes Research and Clinical Practice
Hélène Duval, Laurence Michel-Calemard, Marie Gonzales, Philippe Loget, Claire Beneteau, Annie Buenerd, Madeleine Joubert, Marielee Denis-Musquer, Alix Clemenson, Anne-Laure Chesnais, Sophie Blesson, Isabelle De Pinieux, Anne-Lise Delezoide, Gheorghe Bonyhay, Christine Bellanné-Chantelot, Laurence Heidet, Florence Dupré, Sophie Collardeau-Frachon
OBJECTIVES: To describe macroscopic and microscopic anomalies present in fetuses carrying hepatocyte nuclear factor-1 β mutation, their frequency, and genotype/phenotype correlations. METHODS: Clinical data, ultrasound findings, genetic studies, and autopsy reports of 20 fetal autopsies were analyzed. Histology was reviewed by two pathologists. RESULTS: Macroscopic findings were typically unilateral or bilateral renal enlargement and cortical cysts...
August 2016: Prenatal Diagnosis
Leire Gondra, Stéphane Décramer, Gihad E Chalouhi, Françoise Muller, Rémi Salomon, Laurence Heidet
BACKGROUND: HNF1B mutation is the leading cause of isolated hyperechogenic fetal kidneys with normal or moderately large size. Although most cases have normal amniotic fluid volume, some cases present with early oligohydramnios and renal failure associated with high perinatal mortality. CASE DIAGNOSIS/TREATMENT: Here we report on seven fetuses from six unrelated families, carrying an HNF1B mutation, and presenting with polyhydramnios during the second or third trimester of pregnancy...
October 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Adeline Jacquinet, Debra Millar, Anna Lehman
Ranging from aplastic uterus (including Mayer-Rokitansky-Kuster-Hauser syndrome) to incomplete septate uterus, uterine malformations as a group are relatively frequent in the general population. Specific causes remain largely unknown. Although most occurrences ostensibly seem sporadic, familial recurrences have been observed, which strongly implicate genetic factors. Through the study of animal models, human syndromes, and structural chromosomal variation, several candidate genes have been proposed and subsequently tested with targeted methods in series of individuals with isolated, non-isolated, or syndromic uterine malformations...
August 2016: American Journal of Medical Genetics. Part A
Daan H H M Viering, Jeroen H F de Baaij, Stephen B Walsh, Robert Kleta, Detlef Bockenhauer
Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg(2+)) deficits, as reflected in hypomagnesemia, can cause neuromuscular irritability, seizures and cardiac arrhythmias. With normal Mg(2+) intake, homeostasis is maintained primarily through the regulated reabsorption of Mg(2+) by the thick ascending limb of Henle's loop and distal convoluted tubule of the kidney. Inadequate reabsorption results in renal Mg(2+) wasting, as evidenced by an inappropriately high fractional Mg(2+) excretion...
May 27, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Rhian L Clissold, Charles Shaw-Smith, Peter Turnpenny, Benjamin Bunce, Detlef Bockenhauer, Larissa Kerecuk, Simon Waller, Pamela Bowman, Tamsin Ford, Sian Ellard, Andrew T Hattersley, Coralie Bingham
Heterozygous mutations of the HNF1B gene are the commonest known monogenic cause of developmental kidney disease. Half of patients have a deletion (approximately 1.3 Mb) of chromosome 17q12, encompassing HNF1B plus 14 additional genes. This 17q12 deletion has been linked with an increased risk of neurodevelopmental disorders, such as autism. Here we compared the neurodevelopmental phenotype of 38 patients with HNF1B-associated renal disease due to an intragenic mutation in 18 patients or due to 17q12 deletion in 20 patients to determine whether haploinsufficiency of HNF1B is responsible for the neurodevelopmental phenotype...
July 2016: Kidney International
Jonathan Lerner, Alessia Bagattin, Francisco Verdeguer, Munevver P Makinistoglu, Serge Garbay, Tristan Felix, Laurence Heidet, Marco Pontoglio
Bookmarking factors are transcriptional regulators involved in the mitotic transmission of epigenetic information via their ability to remain associated with mitotic chromatin. The mechanisms through which bookmarking factors bind to mitotic chromatin remain poorly understood. HNF1β is a bookmarking transcription factor that is frequently mutated in patients suffering from renal multicystic dysplasia and diabetes. Here, we show that HNF1β bookmarking activity is impaired by naturally occurring mutations found in patients...
September 30, 2016: Nucleic Acids Research
Wenqian Chen, Arjumand Husain, Gregg S Nelson, Peter F Rambau, Shuhong Liu, Cheng-Han Lee, Sandra Lee, Máire A Duggan, Martin Köbel
Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1...
May 10, 2016: International Journal of Gynecological Pathology
Mengrong Cheng, Xinhong Liu, Mei Yang, Lanchun Han, Aimin Xu, Qingyang Huang
BACKGROUND: Genome-wide association studies (GWAS) of type 2 diabetes (T2D) have discovered a number of loci that contribute to susceptibility to the disease. Future challenges include elucidation of functional mechanisms through which these GWAS-identified loci modulate T2D disease risk. The aim of the present study was to comprehensively characterize T2D associated single nucleotide polymorphisms (SNPs) and genes through computational approaches. METHODS: Computational biology approaches used in the present study included comparative genomic analyses and functional annotation using GWAS3D and RegulomeDB, investigation of the effects of T2D-associated SNPs on miRNA binding and protein phosphorylation, and gene ontology, pathway enrichment, protein-protein interaction (PPI) networks and functional module analysis of T2D-associated genes from previously published GWAS...
April 27, 2016: Journal of Diabetes
Neda Yahoo, Behshad Pournasr, Jalal Rostamzadeh, Mohammad Saeed Hakhamaneshi, Asghar Ebadifar, Fardin Fathi, Hossein Baharvand
Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells...
May 20, 2016: Biochemical and Biophysical Research Communications
Javier González-Peñas, Jorge Amigo, Luis Santomé, Beatriz Sobrino, Julio Brenlla, Santiago Agra, Eduardo Paz, Mario Páramo, Ángel Carracedo, Manuel Arrojo, Javier Costas
There is mounting evidence that regulatory variation plays an important role in genetic risk for schizophrenia. Here, we specifically search for regulatory variants at risk by sequencing promoter regions of twenty-three genes implied in schizophrenia by copy number variant or genome-wide association studies. After strict quality control, a total of 55,206bp per sample were analyzed in 526 schizophrenia cases and 516 controls from Galicia, NW Spain, using the Applied Biosystems SOLiD System. Variants were filtered based on frequency from public databases, chromatin states from the RoadMap Epigenomics Consortium at tissues relevant for schizophrenia, such as fetal brain, mid-frontal lobe, and angular gyrus, and prediction of functionality from RegulomeDB...
July 2016: Schizophrenia Research
Wojciech Fendler, Joanna Madzio, Kamil Kozinski, Kashyap Patel, Justyna Janikiewicz, Magdalena Szopa, Adam Tracz, Maciej Borowiec, Przemyslawa Jarosz-Chobot, Malgorzata Mysliwiec, Agnieszka Szadkowska, Andrew T Hattersley, Sian Ellard, Maciej T Malecki, Agnieszka Dobrzyn, Wojciech Mlynarski
AIMS/HYPOTHESIS: We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1β transcription factor, and investigate whether its effect manifests in serum. METHODS: The Polish cohort (N = 60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 with GCK-MODY, an HbA1c-matched type 1 diabetic group (n = 9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort...
July 2016: Diabetologia
Qiang Hao, Dong Wei, Yaoguang Zhang, Xin Chen, Fan Yang, Ze Yang, Xiaoquan Zhu, Jianye Wang
In the past twenty-five years, over 700 case-control association studies on the risk of prostate cancer have been published worldwide, but their results were largely inconsistent. To facilitate following and explaining these findings, we performed a systematic meta-analysis using allelic contrasts for gene-specific SNVs from at least three independent population-based case-control studies, which were published in the field of prostate cancer between August 1, 1990 and August 1, 2015. Across 66 meta-analyses, a total of 20 genetic variants involving 584,100 subjects in 19 different genes (KLK3, IGFBP3, ESR1, SOD2, CAT, CYP1B1, VDR, RFX6, HNF1B, SRD5A2, FGFR4, LEP, HOXB13, FAS, FOXP4, SLC22A3, LMTK2, EHBP1 and MSMB) exhibited significant association with prostate cancer...
April 19, 2016: Oncotarget
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"