In This Issue

Abstract

see A single center’s experience with noninvasive prenatal testing The rapid uptake of noninvasive prenatal testing (NIPT) has changed patterns of prenatal testing and created complicated genetic counseling scenarios at at least one university-based prenatal diagnosis unit. In a descriptive assessment of the changes brought on by routine use of NIPT in high-risk pregnancies, researchers from the University of North Carolina at Chapel Hill report an unanticipated number of “unclassified” results and higher-than-expected numbers of both false-positive and false-negative results in fetal aneuploidy testing. The sensitivity for detection of aneuploidy in chromosomes 21, 18, and 13 in this clinical setting was lower than that achieved in previous published studies performed in controlled research settings. The current team evaluated results obtained from NIPT aneuploidy tests performed beginning in January 2012, when the test was first offered to pregnant women of advanced maternal age or who had additional risk factors for chromosomal abnormalities. The center tested 208 women over the study period, which ended in September 2012. NIPT detected eight cases of aneuploidy and an additional five cases of “unclassified” abnormal results—an unclassified rate of 11.1%, as compared with 2.8% in prior studies. In three morbidly obese patients, NIPT yielded no result, due to insufficient fetal DNA sample. A false-positive result was obtained in a patient subsequently diagnosed with cancer. Several patients with abnormal ultrasound findings declined invasive testing, opting instead for NIPT. In two of these patients, the NIPT result was normal, yet they delivered neonates diagnosed with aneuploidy. The authors conclude that their findings highlight the importance of counseling patients that NIPT is merely a screening test that does not replace diagnostic testing with amniocentesis or chorionic villus sampling, and that normal NIPT results do not necessarily mean that no other genetic abnormalities are present. —Karyn Hede, News Editor see Nicotinic acetylcholine receptors in human genetic disease In an Invited Review, Christian Schaaf, a medical geneticist at Baylor College of Medicine, Houston, Texas, covers the current understanding of disorders involving nicotinic acetylcholine receptors and the outlook for treatment. Schaaf, winner of the 2013 William K. Bowes Jr Award in Medical Genetics given annually to a promising early-career medical geneticist, explains the relationship between the role of these receptors in rare genetic syndromes and the increasing recognition of the importance of nicotinic acetylcholine receptors in common neurological, behavioral, psychiatric, and neurodegenerative disorders. These pliant and adaptable receptors generally mediate fast (in millisecond time frames) synaptic neurotransmission, and they have been shown to be involved in learning, memory, and attention. Schaaf was among the first to describe the effect of deletions and duplications of the CHRNA7 gene, which encodes for a nicotinic receptor in the brain. Here, he discusses a variety of rare, single-gene disorders involving 1 of the 16 distinct subunits that constitute these receptors, as well as the increasing knowledge of what the genetic mutations and alterations do physiologically. He also discusses their role in relatively common disorders such as depression, attention-deficit hyperactivity disorder, schizophrenia, Alzheimer disease, and Parkinson disease, and he speculates that the development of targeted therapies for common disorders may also benefit those with rare Mendelian disorders. —Karyn Hede, News Editor