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Clinical, histological and genetic characterization of patients with tubular aggregate myopathy caused by mutations in STIM1

18 Oct, 14 | by hqqu

Tubular aggregate myopathies (TAM) are progressive muscle disorders characterized by abnormal accumulations of densely packed membrane tubules on biopsies. The implicated gene STIM1 controls intracellular calcium balance and plays an important role in the regulation of muscle contraction. Here we describe patients with new STIM1 mutations clustering the calcium-binding domain and impairing normal protein function. Patient phenotypes ranged from childhood onset muscle weakness to adult-onset myalgia without muscle weakness, expanding the spectrum associated with this muscle disorder. Our study indicates a genotype/phenotype correlation for tubular aggregate myopathies, and has an important diagnostic relevance. (By Dr. Johann Böhm, http://jmg.bmj.com/content/early/2014/10/17/jmedgenet-2014-102623 )

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OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium

8 Oct, 14 | by hqqu

Pattern dystrophy (PD) of the retinal pigment epithelium is a slowly progressive genetically heterogeneous autosomal dominant disorder. As the name suggests, the disease manifests as changes in the retina that display a certain ‘pattern’. We performed genetic analyses in two families with PD; different approaches that included linkage analysis and whole exome sequencing were used. We identified a novel missense variant (E79K) in OTX2 gene to underlie PD in both families. OTX2 has been previously associated with developmental eye and pituitary anomalies in humans. Our work is the first to associate OTX2 to cause PD and shows that mutations OTX2 can also lead to progressive retinal diseases. (By Dr. Ajoy Vincent, http://jmg.bmj.com/content/early/2014/10/07/jmedgenet-2014-102620 )

Defining and managing incidental findings in genetic and genomic practice

16 Sep, 14 | by hqqu

Our review explored questions about the management and disclosure of incidental genomic findings—those discovered through whole-genome approaches, but unrelated to the question that was asked. We have discussed the various terms used for such findings; factors that determine disclosure; differences in clinical, research and commercial settings; and ethical/practical issues about familial implications and re-contacting testees. Our recommendations include that greater international consensus is developed around disclosure and management; findings are referred to in appropriately different ways according to context; clear consent processes are used, but the absence of consent should not always preclude disclosure; and ways to use the genome output as a resource, accessible over time, are identified, particularly to facilitate disclosure and re-contact when previously unclear findings are clarified. (By Dr Sandi Dheensa, http://jmg.bmj.com/content/early/2014/09/16/jmedgenet-2014-102435 )

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis

2 Sep, 14 | by hqqu

This study identified a SLC17A9 missense variant c.932G>A in a DSAP family by exome sequencing. The c.25C>T variant in additional family supported an important role of SLC17A9 in DSAP.

SLC17A9 encoded a vesicular nucleotide transporter (VNUT), which contributed to ATP vesicle formation and ATP release regulation. The two identified variants located in major facilitator superfamily domain, general substrate transporter. This domain functioned as lycerol-3-phosphate transporter and it consists of 12 transmembrane helix.

The probable mechanism of mutated SLC17A9 in DSAP may be associated with delayed ATP efflux and calcium release into periplasm. (By Dr. Hongzhou Cui, http://jmg.bmj.com/content/early/2014/09/01/jmedgenet-2014-102486 )

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The 2014 International Conference on Intelligent Biology and Medicine

29 Aug, 14 | by hqqu

The 2014 International Conference on Intelligent Biology and Medicine (ICIBM 2014)  will be held on December 4-6, 2014 in San Antonio, TX, USA. Submissions are invited with unpublished original work describing recent advances on all aspects of Bioinformatics, Systems Biology and Intelligent Computing, including, but not restricted to the following topics:

 

Bioinformatics:

•Genomics And Genetics, Including Integrative & Functional Genomics, Genome Evolution

•Next Generation Sequencing Data Analysis, Applications, And Software And Tools

•Big Data Science Including Storage, Analysis, Modeling And Visualization

•Personalized Medicine And Translational Bioinformatics

•Drug Discovery, Design, And Repurposing

•Proteomics, And Protein Structure Prediction, Molecular Simulation And Evolution

•Image Analysis And Processing

 

Systems Biology:

•Modeling and simulation of biological processes, pathways, and networks

•Mathematical and quantitative models of cellular and multi-cellular systems

•Multi-dimensional omics data integration

•Synthetic biological systems

•Metalobolomics

•Self-organization in living systems (cells, organisms, swarms, ecosystems, etc.)

•Applications of systems biology approaches to biomedical studies

 

Intelligent Computing:

•Machine learning, data mining, pattern recognition, and knowledge discovery

•Natural langue processing, literature mining, semantic ontology, data privacy

•Neural computing, kernel methods, feature selection/extraction

•Evolutionary computing, swarm intelligence / optimization, ensemble methods

•Manifold learning theory, artificial life and artificial immune systems

 

Important Dates

Deadline for paper submission  September 1st, 2014

Notification to authors of papers  October 1, 2014

Deadline for highlight paper submission October 1, 2014

Notification to authors of highlight paper October 15, 2014

Deadline for abstract submission October 8, 2014

Notification to authors of abstracts October 15, 2014

Conference early registration October 15, 2014

ICIBM conference December 4-6, 2014

 

 

Travel Awards

Up to 20 travel awards are available to students/postdocs funded by a NSF grant.

 

Victor Jin on behalf of ICIBM 2014 Organizing Committee

CFP_ICIBM2014-extension

Genotype phenotype associations across the voltage-gated sodium channel family

27 Aug, 14 | by hqqu

Mutations in genes which code for sodium ion channel proteins have emerged as the most important genetic factors associated with epilepsy, cardiac rhythm disorders, skeletal muscle channelopathies and pain disorders. Geneticists in partnership with neurologists and cardiologists are often asked to comment on the clinical significance of specific mutations. Comparing over 1300 sodium ion channel mutations in diseases affecting the central and peripheral nervous system, heart and muscle, we have identified many similarities in genetic and clinical characteristics across this ion channel family. These findings should lead to a better understanding of the clinical significance of specific mutations, aiding geneticists and physicians in the interpretation of genetic variants and in counselling individuals and their families. (By Dr Andreas Brunklaus, http://jmg.bmj.com/content/early/2014/08/27/jmedgenet-2014-102608 )

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Titin and desmosomal genes in the natural history of arrhythmogenic right ventricular cardiomyopathy

25 Aug, 14 | by hqqu

Our study investigated the relationship between rare gene variants, clinical features and natural history in arrhythmogenic right ventricular cardiomyopathy. In particular, we explored the phenotype and outcome of rare variant carriers of the giant gene titin and desmosomal genes in a cohort of families with a long-term follow-up, up to 22 years. We found that desmosomal gene rare variant carriers were characterized by a severe prognosis and specific clinical and electrocardiographic features, while titin gene carriers had an intermediate outcome, supraventricular arrhythmias and severe conduction defects, information that may be useful in the clinical practice. (Drs. Francesca Brun and Luisa Mestroni for the authors, http://jmg.bmj.com/content/early/2014/08/25/jmedgenet-2014-102591 )

 

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The two first authors, Francesca Brun , MD, and Carl Barnes, MD, presenting their work at the AHA meeting in Dallas, 2013.

The clinical significance of small copy number variants in neurodevelopmental disorders

8 Aug, 14 | by hqqu

The majority of neuro-developmental disorders (NDDs) such as intellectual disability are likely due to alterations in the genome. It has been shown that about 30% of these patients have losses or gains of large segments of the genome containing many genes or whole chromosomes as in trisomy 21. In this study, we evaluated the contribution of small gains and losses sizing less than 500 kb affecting only few or single genes. We showed that such smaller changes cause NDDs in 2% of patients. In addition, we discovered three novel genetic conditions associated with losses of the genes MED13L, CTNND2 or ACOT7. Our findings are useful for better diagnosis and management of patients with NDDs. (By Prof. Anita Rauch, http://jmg.bmj.com/content/early/2014/08/08/jmedgenet-2014-102588 )

Comprehensive genotype phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation

5 Aug, 14 | by hqqu

Hydatidiform mole (HM) is a human pregnancy with no embryo, but excessive trophoblastic proliferation. Maternal recessive mutationsin NLRP7 are responsible for recurrent HMs, which are characterized by diploid biparental genomes, abnormal DNA methylation, and absence of p57Kip2 expression, the protein coded by the imprinted CDKN1C gene. In this study, we demonstrate a strong correlation between the nature of NLRP7 mutations in the patients and the phenotypical features of their HMs. Protein-truncating mutations repress p57KIP2 expression and are associated with the absence of embryonic tissues and excessive trophoblastic proliferation. However, some missense mutations do not completely repress p57KIP2 expression and are associated with the presence of embryonic tissues and mild trophoblastic proliferation. Our data suggest a novel role for NLRP7in regulating the balance between tissue differentiation and proliferation during early development. (By Ngoc Minh Phuong Nguyen, http://jmg.bmj.com/content/early/2014/08/05/jmedgenet-2014-102546 )

Genetic architectures of ADME genes in five Eurasian admixed populations and implications for drug safety and efficacy

29 Jul, 14 | by hqqu

The genetic heterogeneity can lead to heterogeneous drug responses among individuals, such as less efficacy or unwanted side effects of drug therapy. Moreover, the ethnic/genetic diversity also affects the effective prescription. Here, we investigated the genetic diversity of 282 ADME genes in five northwestern Chinese minority populations which are all admixed people with ancestry contributions from both Eastern and Western Eurasian populations. We revealed that substantial allelic and haplotype differences exist at drug related genes between those minority ethnic groups and Han Chinese, which is likely to violate a single, unified standard of medication in China. (By Dr. Shuhua Xu, http://jmg.bmj.com/content/early/2014/07/29/jmedgenet-2014-102530 )

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