نتایج جستجو برای: missense

تعداد نتایج: 12396  

2015
Ankita Jhuraney Aneliya Velkova Randall C Johnson Bailey Kessing Renato S Carvalho Phillip Whiley Amanda B Spurdle Maaike P G Vreeswijk Sandrine M Caputo Gael A Millot Ana Vega Nicolas Coquelle Alvaro Galli Diana Eccles Marinus J Blok Tuya Pal Rob B van der Luijt Marta Santamariña Pena Susan L Neuhausen Talia Donenberg Eva Machackova Simon Thomas Maxime Vallée Fergus J Couch Sean V Tavtigian J N Mark Glover Marcelo A Carvalho Lawrence C Brody Shyam K Sharan Alvaro N Monteiro

BACKGROUND Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leadi...

2016
Nhu Nguyen Bandana A. Vishwakarma Kevin Oakley Yufen Han Bartlomiej Przychodzen Jaroslaw P. Maciejewski Yang Du

SETBP1 missense mutations have been frequently identified in multiple myeloid neoplasms; however, their oncogenic potential remains unclear. Here we show that expression of Setbp1 mutants carrying two such mutations in mouse bone marrow progenitors efficiently induced development of acute myeloid leukemias (AMLs) in irradiated recipient mice with significantly shorter latencies and greater pene...

Journal: :Human molecular genetics 1999
I Hanson A Churchill J Love R Axton T Moore M Clarke F Meire V van Heyningen

Mutations of the human PAX6 gene underlie aniridia (congenital absence of the iris), a rare dominant malformation of the eye. The spectrum of PAX6 mutations in aniridia patients is highly biased, with 92% of all reported mutations leading to premature truncation of the protein (nonsense, splicing, insertions and deletions) and just 2% leading to substitution of one amino acid by another (missen...

Journal: :Clinical cancer research : an official journal of the American Association for Cancer Research 2004
Christine A Iacobuzio-Donahue Jason Song Giovanni Parmiagiani Charles J Yeo Ralph H Hruban Scott E Kern

PURPOSE AND EXPERIMENTAL DESIGN The mutational spectrum of MADH4 (DPC4/SMAD4) opens valuable insights into the functions of this protein that confer its tumor-suppressive nature in human tumors. We present the MADH4 genetic status determined on a new set of pancreatic, biliary, and duodenal cancers with comparison to the mutational data reported for various tumor types. RESULTS Homozygous del...

Journal: :Gut 2002
M Cravo A J Afonso P Lage C Albuquerque L Maia C Lacerda P Fidalgo P Chaves C Cruz C Nobre-Leitão

BACKGROUND In hereditary non-polyposis colorectal cancer, over 90% of the identified mutations are in two genes, hMSH2 and hMLH1. A large proportion of the mutations detected in these genes are of the missense type which may be either deleterious mutations or harmless polymorphisms. AIM To investigate whether nine missense and one splice site mutation of hMLH1 and hMSH2, in 10 kindreds with a...

Journal: :The Journal of clinical investigation 2006
Kimberly A Risma Robert W Frayer Alexandra H Filipovich Janos Sumegi

Missense mutations in perforin, a critical effector of lymphocyte cytotoxicity, lead to a spectrum of diseases, from familial hemophagocytic lymphohistiocytosis to an increased risk of tumorigenesis. Understanding of the impact of mutations has been limited by an inability to express human perforin in vitro. We have shown, for the first time to our knowledge, that recombinant human perforin is ...

2017
Edward B Li Dawn Truong Shawn A Hallett Kusumika Mukherjee Brian C Schutte Eric C Liao

Large-scale sequencing efforts have captured a rapidly growing catalogue of genetic variations. However, the accurate establishment of gene variant pathogenicity remains a central challenge in translating personal genomics information to clinical decisions. Interferon Regulatory Factor 6 (IRF6) gene variants are significant genetic contributors to orofacial clefts. Although approximately three ...

Journal: :Human molecular genetics 2006
Xiaoli Zhong Jinrong R Liu John W Kyle Dorothy A Hanck William S Agnew

Highly alternatively spliced genes may provide complex targets for disease mutations. Structural changes created by missense mutations may differentially affect the activity of alternative gene products, whereas missense, silent and non-coding mutations may alter developmental regulation of splice variant expression. CACNA1H is a human gene encoding Ca(v)3.2 low-voltage-activated, T-type calciu...

2017
J. Oldenburg C. R. Müller S. Rost M. Watzka C. G. Bevans

Warfarin and other 4-hydroxycoumarinbased oral anticoagulants targeting vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) are administered to humans, mice and rats with different purposes in mind – to act as pesticides in high-dosage baits for killing rodents, but also to save lives when administered in low dosages as antithrombotic drugs in humans. However, high-dosage warfarin used t...

2010
Adam S Mastrocola Christopher D Heinen

The DNA mismatch repair (MMR) pathway is essential in maintaining genomic stability through its role in DNA repair and the checkpoint response. Loss of DNA MMR underlies the hereditary cancer disease Lynch Syndrome (LS). Germline mutations in MSH2 account for approximately 40% of LS patients and of these, 18% are missense variants. One important clinical challenge has been discriminating betwee...

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