Getting personal: Head and neck cancer management in the era of genomic medicine

BackgroundGenetic testing is rapidly becoming an important tool in the management of patients with head and neck cancer. As we enter the era of genomics and personalized medicine, providers should be aware of testing options, counseling resources, and the benefits, limitations, and future of personalized therapy.MethodsThis article offers a primer to assist clinicians treating patients in anticipating and managing the inherent practical and ethical challenges of cancer care in the genomic era.ResultsClinical applications of genomics for head and neck cancer are emerging. We discuss the indications for genetic testing, types of testing available, implications for care, privacy/disclosure concerns, and ethical considerations. Hereditary genetic syndromes associated with head and neck neoplasms are reviewed, and online genetics resources are provided.ConclusionThis article summarizes and contextualizes the evolving diagnostic and therapeutic options that impact the care of patients with head and neck cancer in the genomic era. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2250–E2258, 2016Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137443/1/hed24132.pd

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome

Context: Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. Objective: The objective of this study was to identify a genetic cause of PSIS in an affected child. Methods: Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. Results: We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C.T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A.G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. Conclusions: WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered

Situación actual del cribado neonatal de enfermedades metabólicas en España y en el mundo

Newborn screening programs are key players in a country?s public health strategies, preventing the burden of care associated with the screened disorders. Its importance has dramatically intensified in recent years due to the increasing number of disorders that fulfil criteria for screening. Since the 1960s, many countries implemented newborn screening programs that are now, at least in developed countries, universal, well established, and with excellent results. Nevertheless, much work is still to be done, mainly in developing countries of Africa, Asia, and South America. In some European countries, including Spain, uniformity of screening panels between different regions is still a challenge, being a source of health inequalities between citizens. The authors will present the current status of newborn screening programs in Spain and integrate it into the current European and world scenario.Los programas de cribado neonatal (PCN) son clave en las estrategias de salud pública de una región determinada, establecidas para prevenir los daños asociados a las patologías cribadas. Su importancia se ha intensificado sustancialmente en los últimos años debido al creciente número de trastornos en los que diferentes organismos de evaluación han demostrado el beneficio de su detección temprana para el recién nacido. Desde los años 60-70 del siglo pasado, muchas regiones implementaron de PNC que hoy en día, al menos en los países desarrollados, son universales, bien establecidos y con excelentes resultados. Sin embargo, aún queda mucho por hacer, principalmente en países en vías de desarrollo de África, Asia y América del Sur. En algunos países europeos, incluida España, una mayor uniformidad entre los paneles de cribado de las diferentes regiones continúa siendo un reto, pues conduce a desigualdades en materia de salud. Los autores presentan el estado actual de los PCN en España y lo contextualizan en el escenario real europeo y mundial

Sharing health-related data:A privacy test?

Greater sharing of potentially sensitive data raises important ethical, legal and social issues (ELSI), which risk hindering and even preventing useful data sharing if not properly addressed. One such important issue is respecting the privacy-related interests of individuals whose data are used in genomic research and clinical care. As part of the Global Alliance for Genomics and Health (GA4GH), we examined the ELSI status of health-related data that are typically considered ‘sensitive’ in international policy and data protection laws. We propose that ‘tiered protection’ of such data could be implemented in contexts such as that of the GA4GH Beacon Project to facilitate responsible data sharing. To this end, we discuss a Data Sharing Privacy Test developed to distinguish degrees of sensitivity within categories of data recognised as ‘sensitive’. Based on this, we propose guidance for determining the level of protection when sharing genomic and health-related data for the Beacon Project and in other international data sharing initiatives

A generalized invariant imbedding equation II

Research into fetal development and medicin

The role of disease characteristics in the ethical debate on personal genome testing

Background: Companies are currently marketing personal genome tests directly-to-consumer that provide genetic susceptibility testing for a range of multifactorial diseases simultaneously. As these tests comprise multiple risk analyses for multiple diseases, they may be difficult to evaluate. Insight into morally relevant differences between diseases will assist researchers, healthcare professionals, policy-makers and other stakeholders in the ethical evaluation of personal genome tests. Discussion. In this paper, we identify and discuss four disease characteristics - severity, actionability, age of onset, and the somatic/psychiatric nature of disease - and show how these lead to specific ethical issues. By way of illustration, we apply this framework to genetic susceptibility testing for three diseases: type 2 diabetes, age-related macular degeneration and clinical depression. For these three diseases, we point out the ethical issues that are relevant to the question whether it is morally justifiable to offer genetic susceptibility testing to adults or to children or minors, and on what conditions. Summary. We conclude that the ethical evaluation of personal genome tests is challenging, for the ethical issues differ with the diseases tested for. An understanding of the ethical significance of disease characteristics will improve the ethical, legal and societal debate on personal genome testing