Jeffrey's insights: Jeffrey Modell Foundation's global genetic sequencing pilot program to identify specific primary immunodeficiency defects to optimize disease management and treatment.

Primary immunodeficiencies (PI) are genetic defects of the immune system that result in chronic and often life-threatening infections and/or life-threatening autoimmunity if not diagnosed and treated. Patients with a suspected PI, but without a genetic diagnosis, commonly undergo a diagnostic odyssey that is costly, time-consuming, and arduous. This delay in diagnosis prevents appropriate disease management and treatment, contributing to prolonged suffering and decreased quality of life.

Prevalence of mutations in inherited retinal diseases: A comparison between the United States and India.

Background: Studies evaluating next-generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India).

Methods: This retrospective study of 131 patients who underwent clinically validated targeted NGS or exome sequencing for a wide variety of clinical phenotypes categorized results into a definitive, indeterminate, or negative molecular diagnosis.

Next generation sequencing for clinical diagnostics: Five year experience of an academic laboratory.

Clinical laboratories have adopted next generation sequencing (NGS) as a gold standard for the diagnosis of hereditary disorders because of its analytic accuracy, high throughput, and potential for cost-effectiveness. We describe the implementation of a single broad-based NGS sequencing assay to meet the genetic testing needs at the University of Minnesota. A single hybrid capture library preparation was used for each test ordered, data was informatically blinded to clinically-ordered genes, and identified variants were reviewed and classified by genetic counselors and molecular pathologists.

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk.

Background: Clinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options. Many panels include lesser known breast cancer genes or genes associated with other cancers. The authors hypothesized that using broader gene panels increases the identification of clinically significant findings, some relevant and others incidental to the testing indication.

Pediatric Whole Exome Sequencing: an Assessment of Parents' Perceived and Actual Understanding.

Whole exome sequencing (WES) is an integral tool in the diagnosis of genetic conditions in pediatric patients, but concerns have been expressed about the complexity of the information and the possibility for secondary findings that need to be conveyed to those deciding about WES. Currently, there is no validated tool to assess parental understanding of WES. We developed and implemented a survey to assess perceived and actual understanding of WES in parents who consented to clinical WES for their child between July 2013 and May 2015.

Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience.

Background: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES.

Objective: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered.

Hemophagocytic lymphohistiocytosis in a female patient due to a heterozygous XIAP mutation and skewed X chromosome inactivation.

Genetic forms of hemophagocytic lymphohistiocytosis (HLH) are caused by mutations in autosomal recessive genes affecting perforin-dependent cytotoxic function and two X-linked genes affecting distinct cell signaling pathways: SH2D1A and XIAP. HLH caused by mutations in X-linked genes is typically found only in males. Here we report the occurrence of HLH in a female caused by a heterozygous mutation in XIAP.