The genetics of edmd has expanded the clinical phenotype by documenting the range of findings with mutations in emerin or the gene encoding lamin a and c, lmna. Emerydreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, charcotmarietooth disease, and hutchinsongilford progeria syndrome. To meet this goal, we devised a generic software called umduniversal mutation database. The lmna gene mutations that cause this condition change single amino acids in the lamin a and lamin c proteins. Lmna mutations cause more than 10 types of systemic diseases called laminopathies. Human gene mutation database professional nih library. To date, the umdlmna database comprises 510 different lmna mutations identified in over 2700 individuals, out of which 60% presenting with a laminopathy of the. It aims at making the information readily accessible to anyone interested in the genetic. Methods for analyzing mutations in cancer umd department. Mutations with consequences for mrna splicing are presented in brief with information specifying the relative position of the lesion with respect to a numbered intron donor or acceptor splice site. Laminopathies show striking tissue specificity, with subtypes affecting striated muscle, peripheral. Universal mutation database a generic software to create locusspecific databases lsdbs the umd software includes an optimized structure to assist and secure data entry and to allow the input of a wide range of clinical data. Mutations in the ldl receptor gene ldlr cause familial hypercholesterolemia fh, one of the most frequent hereditary dominant disorders. Knowledge about these mutations and their association with clinical and biological data is essential for clinicians, geneticists, and researchers.
More recently they have been associated with dilated cardiomyopathy dcm and severe forms of arrhythmogenic. The use of such relational dbmss allows to specify. Lmna mutation analysis john welsh cardiovascular diagnostic laboratory the nuclear lamina is formed by a complex network of nuclear lamins, which are type v intermediate filament proteins and can be divided into two classes, type a lamins and type b lamins. Mutations on the lmna gene are responsible for an heterogeneous group of diseases. A generic software to build and analyze locusspecific databases. If you use these data, please refer in your publications to umd lmnaat. The authors suggested that this group of patients may define a new disease entity, which they designated lmnarelated congenital muscular dystrophy. The most common mutation replaces the amino acid arginine at position 527 with the amino acid histidine written as arg527his or r527h. It does not contain information on p53 mutations in animals nor. We therefore developed a locusspecific database software called umdp53.
Seeking for pathomechanical differences to explain the severity of lcmd mutations, we performed an in silico analysis of the umd lmna database and found that lcmd mutations mainly affect. Lmna mutations are most frequently involved in the pathogenesis of dilated cardiomyopathy with conduction disease. Mutations in the lamin ac gene lmna have been associated with several phenotypes ranging from systemic to prevalent of muscle, heart, skin, nerve etc. It encodes four atypes lamins a, ad10, c, c2 via alternative splicing lin et al. What is the abbreviation for universal mutation database. Lamin ac lmna is one of the most frequently mutated genes associated with dilated cardiomyopathy dcm. The goal of this study was to identify lmna mutations, estimate their frequency among polish dilated cardiomyopathy patients and characterize their effect both in vivo and in vitro. The university of utah department of pathology and arup laboratories hosts a growing number of human gene variantdisease database collections. Patient dna is sequenced in both the forward and reverse orientations. Lamin a, encoded by the lmna gene, is a nuclear intermediate filament protein, which is a major constituent of the nuclear lamina lining the eukaryotic inner nuclear membrane. Laminopathies are a clinically heterogeneous group of disorders caused by mutations in lmna. Analysis of sequencing data was carried out using seqscape v2. Is comparable to position but also indicates the type of mutational.
In general, mutation is the main source of genetic variation, which is the raw material for evolution by natural selection. The leiden open source variation database lovd, a freely available webbased software for the collection, display, and curation of dna variants in locusspecific databases lsdbs was developed following the lsdbinabox concept fokkema et al. Because mutations are random changes, they are expected to be mostly deleterious, but some may be beneficial in certain environments. Seeking for pathomechanical differences to explain the severity of lcmd mutations, we performed an in silico analysis of the umdlmna database and found that lcmd mutations mainly affect residues involved in lamin dimer and tetramer stability. Lamin ac assembly defects in lmnacongenital muscular. This database includes 511 references and 3156 subjects, among which 2454 were published position. Mutations in lmna are among the most frequently detected mutations in dcm 3,4, especially in cases with conduction system disease. Human variation databases database oxford academic. Each database relies on both medical and molecular expertise, and uniquely displays sequence variation and. Database of genomic variation and phenotype in humans using ensembl resources database incorporates a suite of tools designed to aid the interpretation of genomic variants dbgap database of genotypes and phenotypes in humans. Positions given as positive integers refer to a 3 downstream location, negative integers refer to a 5. The umd apc database aims at making the information readily accessible to anyone interested in the genetic variations of the apc gene, and to provide an easy way for those who investigate these variations to report their most recent findings.
The basic design criteria included a webbased database system, based on freely available open source software, easy to use and install by. Last update 280814 this database includes 280 references and 3077 mutations 1847 different mutations and 1096 proteic variants in an effort to standardize the information regarding fbn1 mutations, we have created a computerized database that currently contains information about the published mutations of the. Lamins are the only intermediate filaments localized in the nucleus and are thus. Structural instability of lamin a tail domain modulates.
In this study, we describe novel and recurrent emd mutations identified in 18 probands and three carriers from a cohort of 255 north american. Quadriceps myopathy associated with dilated cardiomyopathy has. Limbgirdle muscular dystrophy, or progressive muscle weakness in the absence of contractures, may arise from lmna gene mutations figure 12. Lmna mutations in patients with autosomal dominant edmd occur in the tail and in the 2a rod domain of the protein, suggesting that unique interactions between lamin ac and other nuclear components have an important role in cardiac and skeletal muscle function. Human gene mutation database professional the professional version of the human gene mutation database hgmd provides uptodate information on human inherited gene mutations. The effects of lmna gene mutations in this condition are not well understood. It was developed as a generic software to create locusspecific databases lsdbs with the 4th dimension package from 4d. To collect and analyze these data, we developed a generic software called universal mutation databases.
Umd abbreviation stands for universal mutation database. The umdlmna mutations database was used to identify previously reported lmna sequence variants. The catalog is an academic planning tool and it is the responsibility of every student to be familiar with the information in the catalog. This database compiles all somatic and germline mutations as.
The protein defect was identified in 1973, the gene was loc. I only found information at the gene level cancer consensus genes. Studies the distribution of mutations at the nucleotide level to identify preferential mutation sites. Martin library is here to help you through all stages of your research, from choosing and refining your topic to finding and citing sources. Published and unpublished molecular data are collated from the 14 diagnostic laboratories. For mutation details, use tools available via the mutations button. Between january, 2008 and june, 2012 two patient populations were screened for.
Please look at the gene, the proteins, and the clinics buttons left panel for further details on lmna, lamins ac and laminopathies. Mutations in the lamin ac gene mimic arrhythmogenic right. A major challenge in analyzing the mutations in cancer is distinguishing the handful of driver mutations that cause cancer from the multitude of passenger mutations that play no role in cancer. Provides information about mutations of the apc gene. The umd dmd france database has been set up in a joined national effort through the network of diagnostic laboratories to provide uptodate information about mutations of the dmd gene identified in patients with dystrophinopathies in france.
The dmd mutations database the umd central website. Below are useful links to other sites of interest involved with the dissemination of information in the fields of genetics, mutation research and mutation databases. This database compiles all somatic and germline mutations as well as polymorphisms of the tp53 gene which have been reported in the published literature since 1989, or unpublished data submitted to. Consequently, the future lies not in simple repositories of locusspecific mutations but in dynamic databases linked to various computerized tools for their analysis and that can be directly queried online. The umd software includes an optimized structure to assist and secure data entry and to allow the input of a wide range of clinical. The umd cftr knowledgebaseusing the generic software universal mutation database umd, we have developed the umd cftr knowledgebase to extensively annotate and analyse mutations, variations, haplotypes, complex alleles, genotypes identified in patients by expert laboratories and associated phenotypes. Activation of pdgf pathway links lmna mutation to dilated.
It allows researchers to assess the novelty of identified gene mutations. Where can i find mutation databases specialized in cancer. Lmna mutations in polish patients with dilated cardiomyopathy. Dcm patients with lmna mutations have poor prognosis with lifethreatening ventricular arrhythmias, progression to heart failure and. In part to address this challenge, consortia such as the cancer genome atlas tcga have generated massive catalogues of somatic mutations in thousands of tumors. Novel mutations in lmna ac gene and associated phenotypes. The main proteins encoded by lmna are lamin a and c, which together with lamin b1 and b2, form the nuclear lamina. This free training will be held in the nih library training room, building 10, from 10 to 11. To meet this goal, we devised a generic software called umd universal mutation database. Frontiers modeling skeletal muscle laminopathies using. Somatic p53 mutations in human tumors and cell lines. Study scope is to perform a systematic analysis of the overlapping syndromes so far described and to try to correlate the clinical features to the associated genetic alterations.