journal
MENU ▼
Read by QxMD icon Read
search

Human Mutation

journal
https://www.readbyqxmd.com/read/28608363/misynpat-an-integrated-knowledge-base-linking-clinical-genetic-and-structural-data-for-disease-causing-mutations-in-human-mitochondrial-aminoacyl-trna-synthetases
#1
Luc Moulinier, Raymond Ripp, Gaston Castillo, Olivier Poch, Marie Sissler
Numerous mutations in each of the mitochondrial aminoacyl-tRNA synthetases have been implicated in human diseases. The mutations are autosomal and recessive and lead mainly to neurological disorders, although with pleiotropic effects. The processes and interactions that drive the etiology of the disorders associated with mitochondrial aminoacyl-tRNA synthetases are far from understood. The complexity of the clinical, genetic and structural data requires concerted, interdisciplinary efforts to understand the molecular biology of these disorders...
June 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/28603918/cftr-france-a-national-relational-patient-database-for-sharing-genetic-and-phenotypic-data-associated-with-rare-cftr-variants-a
#2
Mireille Claustres, Corinne Theze, Marie des Georges, David Baux, Emmanuelle Girodon, Thierry Bienvenu, Marie-Pierre Audrezet, Ingrid Dugueperoux, Claude Ferec, Guy Lalau, Adrien Pagin, Alain Kitzis, Vincent Thoreau, Véronique Gaston, Eric Bieth, Marie-Claire Malinge, Marie-Pierre Reboul, Patricia Fergelot, Lydie Lemonnier, Chadia Mekki, Pascale Fanen, Anne Bergougnoux, Souphatta Sasorith, Caroline Raynal, Corinne Bareil
Most of 2,000 variants identified in the CFTR (cystic fibrosis transmembrane regulator) gene are rare or private. Their interpretation is hampered by the lack of available data and resources, making patient care and genetic counseling challenging. We developed a patient-based database dedicated to the annotations of rare CFTR variants in the context of their cis- and trans-allelic combinations. Based on almost 30 years' experience of CFTR testing, CFTR-France (https://cftr.iurc.montp.inserm.fr/cftr) currently compiles 16,819 variant records from 4,615 individuals with cystic fibrosis (CF) or CFTR-RD (related disorders), fetuses with ultrasound bowel anomalies, newborns awaiting clinical diagnosis and asymptomatic compound heterozygotes...
June 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/28600868/deep-bipolar-identifying-genomic-mutations-for-bipolar-disorder-via-deep-learning
#3
Sundaram Laksshman, Rajendra Rana Bhat, Vivek Viswanath, Xiaolin Li
Bipolar disorder (BD), also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression and over-excitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from BD. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to conventional lengthy and costly post-symptom clinical diagnosis...
June 10, 2017: Human Mutation
https://www.readbyqxmd.com/read/28598576/semi-automated-cancer-genome-analysis-using-high-performance-computing
#4
Giuliano Crispatzu, Pranav Kulkarni, Mohammad R Toliat, Peter Nürnberg, Marco Herling, Carmen D Herling, Peter Frommolt
Next-Generation Sequencing (NGS) has turned from a new and experimental technology into a standard procedure for cancer genome studies and clinical investigation. While a multitude of software packages for cancer genome data analysis have been made available, these need to be combined into efficient analytical workflows that cover multiple aspects relevant to a clinical environment and that deliver handy results within a reasonable time frame. Here, we introduce QuickNGS Cancer as a new suite of bioinformatics pipelines which is focused on cancer genomics and significantly reduces the analytical hurdles that still limit a broader applicability of NGS technology, particularly to clinically driven research...
June 9, 2017: Human Mutation
https://www.readbyqxmd.com/read/28585352/a-rab27a-duplication-in-several-cases-of-griscelli-syndrome-type-2-an-explanation-for-cases-lacking-a-genetic-diagnosis
#5
Virginie Grandin, Fernando E Sepulveda, Nathalie Lambert, Mofareh Al Zahrani, Eman Al Idrissi, Hamoud Al-Mousa, Fahd Almanjomi, Abdulaziz Al-Ghonaium, Murad K Habazi, Hamza A Alghamdi, Capucine Picard, Christine Bole-Feysot, Patrick Nitschke, Gael Ménasché, Geneviève de Saint Basile
Griscelli syndrome type 2 (GS2) is a rare and often fatal autosomal recessive, hyperinflammatory disorder. It is associated with hypopigmentation of the skin and the hair, resulting in the characteristic pigment accumulation and clumping in the hair shaft. Loss-of function mutations in RAB27A, resulting from point mutations, short indel or large deletions, account for all the cases reported to date. However, several GS2 cases originating from Saudi Arabia lack a genetic diagnosis. Here, we report on a new RAB27A genetic anomaly, observed in seven Saudi Arabia families that had remained negative after extensive molecular genomic DNA testing...
June 6, 2017: Human Mutation
https://www.readbyqxmd.com/read/28585349/csnk2b-splice-site-mutations-in-patients-cause-intellectual-disability-with-or-without-myoclonic-epilepsy
#6
Karine Poirier, Laurence Hubert, Géraldine Viot, Marlène Rio, Pierre Billuart, Claude Besmond, Thierry Bienvenu
De novo mutations are a frequent cause of disorders related to brain development. We report the results from the screening of two patients diagnosed with intellectual disability (ID) using exome sequencing to identify new causative de novo mutations. Exome sequencing was conducted in two patient-parent trios to identify de novovariants. In silico and expression studies were also performed to evaluate the functional consequences of these variants.The two patients presented developmental delay with minor facial dysmorphy...
June 6, 2017: Human Mutation
https://www.readbyqxmd.com/read/28585318/hermansky-pudlak-syndrome-type-2-aberrant-pre-mrna-splicing-and-mislocalization-of-granule-proteins-in-neutrophils
#7
Martin de Boer, Karin van Leeuwen, Judy Geissler, Floris van Alphen, Esther de Vries, Martijn van der Kuip, Suzanne W J Terheggen, Hans Janssen, Timo K van den Berg, Alexander B Meijer, Dirk Roos, Taco W Kuijpers
Hermansky-Pudlak syndrome type 2 (HPS2) is a syndrome caused by mutations in the beta-3A subunit of the adaptor protein (AP)-3 complex (AP3B1 gene). We describe five unreported cases with four novel mutations, one of which caused aberrant pre-mRNA splicing. A point mutation c.2702C>G in exon 23 of the AP3B1 gene caused deletion of 112 bp in the mRNA in two siblings. This mutation activates a cryptic donor splice site that overrules the wild-type donor splice site of this exon. Three other novel mutations in AP3B1 were identified, that is, a nonsense mutation c...
June 6, 2017: Human Mutation
https://www.readbyqxmd.com/read/28581210/reduced-cell-surface-levels-of-gpi-linked-markers-in-a-new-case-with-pigg-loss-of-function
#8
Jin James Zhao, Jonatan Halvardson, Alexej Knaus, Patrik Georgii-Hemming, Peter Baeck, Peter Krawitz, Ann-Charlotte Thuresson, Lars Feuk
Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability, seizures and facial dysmorphism. Here we present two siblings with intellectual disability, cerebellar hypoplasia, cerebellar ataxia, early onset seizures and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178...
June 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28556356/identification-of-a-functional-enhancer-variant-within-the-chronic-pancreatitis-associated-spink1-c-101a-g-p-asn34ser-containing-haplotype
#9
Arnaud Boulling, Emmanuelle Masson, Wen-Bin Zou, Sumit Paliwal, Hao Wu, Prachand Issarapu, Seema Bhaskar, Emmanuelle Génin, David N Cooper, Zhao-Shen Li, Giriraj R Chandak, Zhuan Liao, Jian-Min Chen, Claude Férec
The haplotype harboring the SPINK1 c.101A>G (p.Asn34Ser) variant (also known as rs17107315:T>C) represents the most important heritable risk factor for idiopathic chronic pancreatitis identified to date. The causal variant contained within this risk haplotype has however remained stubbornly elusive. Herein, we set out to resolve this enigma by employing a hypothesis-driven approach. First, we searched for variants in strong linkage disequilibrium (LD) with rs17107315:T>C using HaploReg v4.1. Second, we identified two candidate SNPs by visual inspection of sequences spanning all 25 SNPs found to be in LD with rs17107315:T>C, guided by prior knowledge of pancreas-specific transcription factors and their cognate binding sites...
May 29, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544139/rettbase-rett-syndrome-database-update
#10
Rahul Krishnaraj, Gladys Ho, John Christodoulou
Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of RTT. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to RTT, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities. While the genetic basis for the RTT has been recognized, so far there is no effective cure for the disease and the treatments available are mainly aimed at ameliorating clinical problems associated with the disorder...
May 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544272/ensemble-variant-interpretation-methods-to-predict-enzyme-activity-and-assign-pathogenicity-in-the-cagi4-naglu-human-n-acetyl-glucosaminidase-and-ube2i-human-sumo-ligase-challenges
#11
Yizhou Yin, Kunal Kundu, Lipika R Pal, John Moult
CAGI (Critical Assessment of Genome Interpretation) conducts community experiments to determine the state of the art in relating genotype to phenotype. Here we report results obtained using newly-developed ensemble methods to address two CAGI4 challenges: enzyme activity for population missense variants found in NAGLU (Human N-acetyl-glucosaminidase) and random missense mutations in Human UBE2I (Human SUMO E2 ligase), assayed in a high throughput competitive yeast complementation procedure. The ensemble methods are effective, ranked 2(nd) for SUMO-ligase and 3(rd) for NAGLU, according to the CAGI independent assessors...
May 24, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544481/matching-phenotypes-to-whole-genomes-lessons-learned-from-four-iterations-of-the-personal-genome-project-community-challenges
#12
Binghuang Cai, Biao Li, Nikki Kiga, Janita Thusberg, Timothy Bergquist, Yun-Ching Chen, Noushin Niknafs, Hannah Carter, Collin Tokheim, Violeta Beleva-Guthrie, Christopher Douville, Rohit Bhattacharya, Hui Ting Grace Yeo, Jean Fan, Sohini Sengupta, Dewey Kim, Melissa Cline, Tychele Turner, Mark Diekhans, Jan Zaucha, Lipika R Pal, Chen Cao, Chen-Hsin Yu, Yizhou Yin, Marco Carraro, Manuel Giollo, Carlo Ferrari, Emanuela Leonardi, Silvio C E Tosatto, Jason Bobe, Madeleine Ball, Roger Hoskins, Susanna Repo, George Church, Steven E Brenner, John Moult, Julian Gough, Mario Stanke, Rachel Karchin, Sean D Mooney
The advent of next generation sequencing has dramatically decreased the cost for whole genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544275/recessive-mutations-in-msto1-cause-mitochondrial-dynamics-impairment-leading-to-myopathy-and-ataxia
#13
Alessia Nasca, Chiara Scotton, Irina Zaharieva, Marcella Neri, Rita Selvatici, Olafur Thor Magnusson, Aniko Gal, David Weaver, Rachele Rossi, Annarita Armaroli, Marika Pane, Rahul Phadke, Anna Sarkozy, Francesco Muntoni, Imelda Hughes, Antonella Cecconi, György Hajnóczky, Alice Donati, Eugenio Mercuri, Massimo Zeviani, Alessandra Ferlini, Daniele Ghezzi
We report here the first families carrying recessive variants in the MSTO1 gene: compound heterozygous mutations were identified in two sisters and in an unrelated singleton case, who presented a multisystem complex phenotype mainly characterized by myopathy and cerebellar ataxia. Human MSTO1 is a poorly studied protein, suggested to have mitochondrial localization and to regulate morphology and distribution of mitochondria. As for other mutations affecting genes involved in mitochondrial dynamics, no biochemical defects typical of mitochondrial disorders were reported...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544059/objective-assessment-of-the-evolutionary-action-equation-for-the-fitness-effect-of-missense-mutations-across-cagi-blinded-contests
#14
Panagiotis Katsonis, Olivier Lichtarge
A major challenge in genome interpretation is to estimate the fitness effect of coding variants of unknown significance (VUS). Labor, limited understanding of protein functions, and lack of assays generally limit direct experimental assessment of VUS, and make robust and accurate computational approaches a necessity. Often, however, algorithms that predict mutational effect disagree among themselves and with experimental data, slowing their adoption for clinical diagnostics. To objectively assess such methods, the Critical Assessment of Genome Interpretation (CAGI) community organizes contests to predict unpublished experimental data, available only to CAGI assessors...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28543983/mutation-of-serine-threonine-protein-kinase-36-stk36-causes-primary-ciliary-dyskinesia-with-a-central-pair-defect
#15
Christine Edelbusch, Sandra Cindrić, Gerard W Dougherty, Niki T Loges, Heike Olbrich, Joseph Rivlin, Julia Wallmeier, Petra Pennekamp, Israel Amirav, Heymut Omran
Primary ciliary dyskinesia (PCD) is a genetic condition of impaired ciliary beating, characterized by chronic infections of the upper and lower airways and progressive lung failure. Defects of the outer dynein arms are the most common cause of PCD. In about half of the affected individuals, PCD occurs with situs inversus (Kartagener syndrome). A minor PCD subgroup including defects of the radial spokes (RS) and central pair (CP) is hallmarked by the absence of laterality defects, subtle beating abnormalities, and unequivocally apparent ultrastructural defects of the ciliary axoneme, making their diagnosis challenging...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28512778/cagi4-crohn-s-exome-challenge-marker-snp-versus-exome-variant-models-for-assigning-risk-of-crohn-disease
#16
Lipika R Pal, Kunal Kundu, Yizhou Yin, John Moult
Understanding the basis of complex trait disease is a fundamental problem in human genetics. The CAGI Crohn's Exome challenges are providing insight into the adequacy of current disease models by requiring participants to identify which of a set of individuals has been diagnosed with the disease, given exome data. For the CAGI4 round, we developed a method that used the genotypes from exome sequencing data only to impute the status of Genome Wide Association Studies (GWAS) marker single nucleotide polymorphisms (SNPs)...
May 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/28512758/reporting-practices-for-unsolicited-and-secondary-findings-from-next-generation-sequencing-technologies-perspectives-of-laboratory-personnel
#17
Danya F Vears, Karine Sénécal, Pascal Borry
While next-generation sequencing (NGS) has enormous potential to identify genetic causes of disease, the nature of the technology means that it can also identify additional information about the individual receiving sequencing that is unrelated to the original rationale for testing. Reporting these unsolicited findings (UF) to clinicians, and subsequently to patients, could lead to potentially lifesaving interventions. Most international guidelines provide limited specific recommendations as to whether these UF should be reported...
May 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/28512736/cagi4-sickkids-clinical-genomes-challenge-a-pipeline-for-identifying-pathogenic-variants
#18
Lipika R Pal, Kunal Kundu, Yizhou Yin, John Moult
Compared with earlier more restricted sequencing technologies, identification of rare disease variants using whole genome sequence has the possibility of finding all causative variants, but issues of data quality and an overwhelming level of background variants complicate the analysis. The CAGI4 SickKids clinical genome challenge provided an opportunity to assess the landscape of variants found in a difficult set of 25 unsolved rare disease cases. To address the challenge, we developed a three-stage pipeline, first carefully analyzing data quality, then classifying high quality gene specific variants into seven categories, and finally examining each candidate variant for compatibility with the often complex phenotypes of these patients for final prioritization...
May 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/28508593/missense-variant-pathogenicity-predictors-generalize-well-across-a-range-of-function-specific-prediction-challenges
#19
Vikas Pejaver, Sean D Mooney, Predrag Radivojac
The steady advances in machine learning and accumulation of biomedical data have contributed to the development of numerous computational models that assess the impact of missense variants. Different methods, however, operationalize impact differently. Two common tasks in this context are the prediction of the pathogenicity of variants and the prediction of their effects on a protein's function. These are related but distinct problems, and it is unclear whether methods developed for one are optimized for the other...
May 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/28503910/postzygotic-single-nucleotide-mosaicisms-contribute-to-the-etiology-of-autism-spectrum-disorder-and-autistic-traits-and-the-origin-of-mutations
#20
Yanmei Dou, Xiaoxu Yang, Ziyi Li, Sheng Wang, Zheng Zhang, Adam Yongxin Ye, Linlin Yan, Changhong Yang, Qixi Wu, Jiarui Li, Boxun Zhao, August Yue Huang, Liping Wei
The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF) pSNMs with a high mutant allele fraction (MAF≥ 0...
May 14, 2017: Human Mutation
journal
journal
31178
1
2
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"