A JAMA THEME ISSUE
Edited by W. Gregory Feero, MD, PhD
Long QT syndrome (LQTS) has been implicated in up to 10% of sudden infant death syndrome cases and may contribute to sudden, unexpected fetal mortality. In a postmortem molecular genetic evaluation of 91 cases of unexplained intrauterine fetal death (IUFD), Crotti and colleagues found mutations associated with LQTS susceptibility in 3 cases (3.3%) and genetic variants leading to dysfunctional LQTS-associated ion channels in 8 cases (8.8%). In an editorial, Guttmacher and colleagues discuss LQTS susceptibility mutations and pregnancy loss.
See Article and Editorial
Gene variants associated with risk of late-onset Alzheimer disease in persons of European ancestry have been identified. Whether these same variants are also associated with Alzheimer disease risk in African Americans is unknown. In a meta-analysis of genome-wide data from 1968 African Americans with late-onset Alzheimer disease and 3928 elderly and cognitively normal African American controls, Reitz and colleagues found that ABCA7 gene variants and other genes (including APOE ϵ4) associated with increased risk of Alzheimer disease among individuals of European ancestry were also associated with disease risk in African Americans. In an editorial, Nussbaum discusses personal genomics and the genetics of complex diseases.
See Article, Editorial,
The BRAF V600E mutation is a prominent oncogene in papillary thyroid cancer. In a retrospective multicenter study involving 1849 patients with papillary thyroid cancer, Xing and colleagues found that presence of the BRAF V600E mutation was associated with increased cancer-related mortality. However, mortality in papillary thyroid cancer is low, and after adjusting for features of aggressive tumors (metastasis, extrathyroidal invasion), the association was no longer significant. In an editorial, Cappola and Mandel discuss molecular testing in thyroid cancer.
In a retrospective investigation that analyzed 45 fecal samples (from 34 patients) obtained during a Shiga-toxigenic Escherichia coli (STEC) O104:H4 outbreak, Loman and colleagues assessed the potential of a metagenomics approach—involving direct sequencing of DNA extracted from the pooled samples—to identify and characterize the outbreak strain. The authors report recovery of a draft genome sequence of the outbreak STEC strain. In subsequent phases of the study, they detected sequences of the Shiga-toxin genes in 27 of 40 STEC-positive samples and also recovered and identified gene sequences from 4 bacterial pathogens other than the outbreak strain. In an editorial, Relman discusses the application of metagenomics in infectious disease diagnosis and outbreak investigation.
Korf and Rehm review clinical application of new approaches to genetic and genomic testing of rare and common disorders. Their discussion highlights several key issues in clinical genetic testing, including analytic validity; clinical validity; clinical utility; and ethical, legal, and social issues.
Researchers are using genomic analyses to study the body's microbial communities and their contributions to health and disease.
Realizing the opportunities of genomics
Professional judgment in genomic medicine
Genomic medicine and health IT
Accessing genomic medicine
“[W]hile physicians rely on personal and family histories to help make diagnoses, these clinical tools are by no means perfect.” From “Preparing for the 21st-Century Patient.”
Dr Feero discusses the medical innovation of genetics research.
A glossary to facilitate your reading.
Dr Feero summarizes and comments on this week's issue. Go to
For your patients: Information about genomic medicine.
This Week in JAMA. JAMA. 2013;309(14):1433. doi:10.1001/jama.2012.145357