Showing papers in "Genetics in Medicine in 2015"

TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.

TL;DR: The utility of family-based exome sequencing and analysis is demonstrated to obtain the highest reported detection rate in an unselected clinical cohort, illustrating the utility of diagnosticExome sequencing as a transformative technology for the molecular diagnosis of genetic disease.

TL;DR: The purpose of this practice guideline is to present a single set of comprehensive personal and family history criteria to facilitate identification and maximize appropriate referral of at-risk individuals for cancer genetic consultation.

TL;DR: This statement is intended for physicians who are engaged in diagnosing and treating patients with suspected or demonstrated mitochondrial disease and to provide recommendations for optimal diagnosis and treatment.

TL;DR: Clinical HCM genetic testing provides a definitive molecular diagnosis for many patients and provides cost savings to families, and an expanded gene panel encompassing more than 50 genes identified only a very small number of additional pathogenic variants beyond those identifiable in the original panels.

TL;DR: A testing algorithm is proposed to help clinicians opt for the most appropriate molecular diagnostic tool for each scenario, and current limitations of next-generation sequencing technology and variant interpretation capabilities caution us against offering exome sequencing or genome sequencing as either stand-alone or first-choice diagnostic approaches.

TL;DR: It is suggested that some cases resolved by whole-exome sequencing will have direct therapeutic implications, and the application of appropriate bioinformatics analyses to clinical sequence data can also help implicate novel disease genes and suggest expanded phenotypes for known disease genes.

TL;DR: The first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS are presented.

TL;DR: Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer, which contains at least two affected first-degree relatives.

TL;DR: Based on quantified performance metrics, the data suggest that selective targeted enrichment is preferable to whole-exome sequencing for genetic diagnostic testing of patients with inherited eye disorders.

TL;DR: Although studies reported that primary-care providers perceive genetics as being important, barriers to the integration of genetics medicine into routine patient care were identified and the promotion of practical guidelines, point-of-care risk assessment tools, tailored educational tools, and other systems-level strategies will assist primary-Care providers in providing genetics services for their patients.

TL;DR: The data underscore the importance of COL4A1 andCOL4A2 mutations in cerebrovascular disease, also in sporadic patients and propose a screening protocol at diagnosis.

TL;DR: The identification of novel genotype–phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments ofIRD patients.

TL;DR: These data demonstrate that massively parallel sequencing identifies reportable variants in known cancer susceptibility genes in more than 30% of patients with early-onset breast cancer, however, only few patients have definitively actionable mutations given current clinical management guidelines.

TL;DR: In this paper, the authors analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and cerebral cavernous malformation lesion lesion burden.

TL;DR: The results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45–90 repeat alleles.

TL;DR: Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history–based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.

TL;DR: Returning incidental findings is likely cost-effective for certain patient populations and screening of generally healthy individuals is likely not cost- effective based on current data, unless next-generation sequencing costs less than $500.

TL;DR: The 15q13.3 microdeletion syndrome is predominantly characterized by neuropsychiatric expression, and there are implications for pre- and postnatal detection, genetic counseling, and anticipatory care.

TL;DR: A bioinformatics approach to extract CNV information from whole-exome sequencing and its utility in clinical testing is described and the clinical utility of single-exon resolution in CNV assays is demonstrated.

TL;DR: Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/ or oligo–single-nucleotide polymorphism microarray was evaluated.

TL;DR: All previously reported SDH mutations were collected with the aim of defining their nature and tumor spectrum and bioinformatics analysis using SIFT, Polyphen2, and Mutation Assessor to predict the functional impact of nonsynonymous mutations.

TL;DR: New potential colorectal cancer predisposition variants in genes that have a role incancer predisposition and are involved in DNA repair and the cell cycle are identified, which supports their putative involvement in germ-line predisposition to this neoplasm.

TL;DR: Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer.

TL;DR: Examination of genetics curricula in US and Canadian medical schools to ascertain whether and how curricula are keeping pace with rapid evolution of genomic technologies provides an important update on how genetics and genomics is taught at US andCanadian medical schools.

TL;DR: A systematic literature search on the ethical, legal, social, and practical issues involved in recontacting former patients who received genetic services indicates that most but not all patients value being recontacted, and focuses on the question of in what situations recontacts might be regarded as good standard of care.

TL;DR: The overall increased access made possible with telephone genetic counseling should be considered in light of the possibility that this may also lead to lower rates of testing among high-risk minority women, and additional care should be taken to address potential barriers when services are delivered by telephone.

TL;DR: These aortic event– and age-associated findings may have important implications for the management of Marfan syndrome patients with FBN1 truncating and splicing variants.

TL;DR: The genotype data and annotated copy-number variations for this largely Caucasian population will represent a valuable public resource enabling clinical genetics research and diagnostics.

TL;DR: Examining how stakeholder engagement is used to develop policies in genomics research and public health areas is examined, as well as to identify future priorities for conducting evidence-based stakeholder engagements.