[Show abstract][Hide abstract]ABSTRACT: The cover, by Ian D. Krantz, features a composite image from several of his articles including the Introduction Dr. Laird G. Jackson Festschrift, DOI: 10.1002/ajmg.c.31499.
Article · Jun 2016 · American Journal of Medical Genetics Part C Seminars in Medical Genetics
[Show abstract][Hide abstract]ABSTRACT: The introduction of diagnostic clinical genome and exome sequencing (CGES) is changing the scope of practice for clinical geneticists. Many large institutions are making a significant investment in infrastructure and technology, allowing clinicians to access CGES, especially as health-care coverage begins to extend to clinically indicated genomic sequencing-based tests. Translating and realizing the comprehensive clinical benefits of genomic medicine remain a key challenge for the current and future care of patients. With the increasing application of CGES, it is necessary for geneticists and other health-care providers to understand its benefits and limitations in order to interpret the clinical relevance of genomic variants identified in the context of health and disease. New, collaborative working relationships with specialists across diverse disciplines (e.g., clinicians, laboratorians, bioinformaticians) will undoubtedly be key attributes of the future practice of clinical genetics and may serve as an example for other specialties in medicine. These new skills and relationships will also inform the development of the future model of clinical genetics training curricula. To address the evolving role of the clinical geneticist in the rapidly changing climate of genomic medicine, two Clinical Genetics Think Tank meetings were held that brought together physicians, laboratorians, scientists, genetic counselors, trainees, and patients with experience in clinical genetics, genetic diagnostics, and genetics education. This article provides recommendations that will guide the integration of genomics into clinical practice.Genet Med advance online publication 12 May 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.17.
[Show abstract][Hide abstract]ABSTRACT: Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
Article · May 2016 · The American Journal of Human Genetics
[Show abstract][Hide abstract]ABSTRACT: Background:
Pallister-Killian syndrome (PKS) is a prototypic mosaic aneuploidy syndrome caused by mosaic supernumerary marker isochromosome 12p. Cells possessing the isochromosome 12p rapidly diminish after birth in the peripheral blood, often necessitating a skin biopsy for diagnosis. Therefore, a genomic testing that is capable of detecting low percent mosaic isochromosome 12p is preferred for the diagnosis of PKS.
The utility of the droplet digital PCR system in quantifying the mosaic ratio of isochromosome 12p in PKS was evaluated.
Droplet digital PCR was able to precisely quantify isochromosome 12p mosaic ratio, and copy number measured by droplet digital PCR was correlated well with that of fluorescence in situ hybridization analysis.
Droplet digital PCR should be considered as an effective tool for both clinical and research analytics to precisely quantify mosaic genomic copy number alterations or mosaic mutations.