Showing papers in "Genetics in Medicine in 2014"

TL;DR: Treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenyalanine in the range of 120–360 µmol/l, and any interventions, including medications, or combination of therapies that help to achieve that goal in an individual, without other negative consequences, should be considered appropriate therapy.

TL;DR: This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys–Dietz syndrome.

TL;DR: The data point to an important role for targeted multigene panels in diagnosing hereditary cancer predisposition, particularly for patients with clinical histories spanning several possible diagnoses and for Patients with suspicious clinical histories not meeting diagnostic criteria for a specific hereditary cancer syndrome.

TL;DR: This guideline helps health-care providers recognize patients with all forms of GSD I, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management.

TL;DR: The data illustrate the utility of broad gene panels for genetically and clinically heterogeneous diseases but also highlight challenges as molecular diagnostics moves toward genome-wide testing.

TL;DR: Estimating a 50% success rate for next-generation sequencing in undiagnosed genetic disorders, its application after the first clinical visit could result in a higher rate of genetic diagnosis at a considerable cost savings per successful diagnosis.

TL;DR: This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling.

TL;DR: The results show that whole-exome sequencing is feasible, has clinical usefulness, and allows timely medical interventions, informed reproductive choices, and avoidance of additional testing.

TL;DR: Although vascular Ehlers–Danlos syndrome appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1, these findings indicate that when counseling families, confirmation of the presence of a COL 3A1 mutation and its nature can help evaluate the risks of complications.

TL;DR: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum–associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease.

TL;DR: The potential contribution of cell line–specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening for fetal aneuploidy is calculated, suggesting underlying biologic mechanisms will never allow 100% sensitivity or specificity.

TL;DR: Evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking and recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys.

TL;DR: While celebrities can bring heightened awareness to health issues, there is a need for these messages to be accompanied by more purposeful communication efforts to assist the public in understanding and using the complex diagnostic and treatment information that these stories convey.

TL;DR: To assist clinical laboratories in developing and validating testing for this group of inherited colorectal cancers, the American College of Medical Genetics and Genomics has developed the following technical standards and guidelines.

TL;DR: Assessment of the accuracy of next-generation sequencing variant identification in a clinical genomics laboratory established a quality score threshold for confirmatory Sanger-based testing, predicting that going forward, the volume of Sanger confirmation can be reduced, alleviating a significant amount of the labor and cost burden on clinical laboratories wishing to use next- generation sequencing technology.

TL;DR: Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered clinically without the need for customized test development.

TL;DR: The National Human Genome Research Institute has convened the Inter-Society Coordinating Committee for Physician Education in Genomics (ISCC) to develop and share best practices in the use of genomics in medicine.

TL;DR: A delay between symptom onset and treatment exists, especially in patients with attenuated mucopolysaccharidosis I, and a better understanding of disease manifestations may help facilitate prompt diagnosis and treatment and improve patient outcomes.

TL;DR: This review provides basic insights into some of the most popular in silico tools for splicing defect prediction, from the viewpoint of end users, and focuses on those tools whose primary goal is to predict the impact of mutations within the 5′ and 3′ splicing consensus regions.

TL;DR: The risk of pregnancy-related complications is increased in women with vascular Ehlers–Danlos syndrome compared with the general population; however, survival data indicate that pregnancy does not appear to affect overall mortality compared with nulliparous women with CVS.

TL;DR: The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominate conditions.

TL;DR: Region 4 Stork interpretive tools, second-tier tests, and other evidence-based interpretation rules could have reduced false-positive cases by up to 90% in California.

TL;DR: Preliminary data regarding the preferences for secondary findings results disclosure based on the first 200 families referred to Ambry Genetics for diagnostic exome sequencing are provided, for the first time, and represent the unprecedented results of a large reference laboratory providing clinicalExome sequencing.

TL;DR: Many personalized medicine tests have been found to be relatively cost-effective, although fewer have beenFindings indicate that testing provides better health although at higher cost, with almost half of the ratios falling below $50,000 per quality-adjusted life year gained.

TL;DR: Males with Lynch syndrome had a nearly fivefold increased risk of developing prostate cancer but did not appear to have earlier onset or a more aggressive phenotype.

TL;DR: These data suggest that support for broad consent is contingent on sufficient information about data use, and work with research participants and community leaders to understand, respond to, and influence opinions about a given, ongoing study may improve uptake of broad consent.

TL;DR: The Mayo Muir–Torre syndrome risk scoring system appears to identify whether patients who present with sebaceous neoplasms are in need of further Lynch syndrome evaluation using easily ascertained clinical information.

TL;DR: Next-generation sequencing combined with microarrays provides the diagnosis for approximately half of the GJB2 mutation–negative individuals, and Usher syndrome was found to be more frequent in the study cohort than anticipated.

TL;DR: Many parents of children in pediatric genomic research indicated a strong desire to receive a broader range of results than is described in consensus recommendations, and clear delineation of what will be offered should be established at the time of consent.

TL;DR: Given the rapid growth of genetic information available in both disease and normal populations, periodic reassessment of single-nucleotide variant data is essential in hypertrophic cardiomyopathy.