A New Next-Generation Sequencing-Based Assay for Concurrent Preimplantation Genetic Diagnosis of Charcot-Marie-Tooth Disease Type 1A and Aneuploidy Screening

Charcot-Marie-Tooth （CMT） disease is the most common hereditary neuropathy, with a population prevalence of 1 in 2500. CMT disease type 1A （CMT1A）, accounting for ~70% of CMT1 cases and ~ 50% of all CMT cases, is transmitted in an autosomal dominant manner. CMT1A maps to chromo- some 17pl 1.2 and is caused, in the majority of cases, by a 1.4- Mb tandem duplication that includes the peripheral myelin protein22 （PMP22） gene （Li et al., 2013）. The disease usually presents in the first 20 years of age, causing difficulty in walking or running, distal symmetrical muscle weakness and wasting, and sensory loss （van Paassen et al., 2014）.

Pregnancy and child developmental outcomes after preimplantation genetic screening: a meta-analytic and systematic review

Background In in vitro fertilization (IVF) treatment, preimplantation genetic diagnosis/screening (PGD/S) attempts to detect chromosomal abnormalities in embryos before implantation. Using the meta-analytic and qualitative review approaches, this study aims to evaluate the effect of PGD/S on clinical pregnancy, live births, and childhood outcomes. Methods We conducted a literature search using 1) PubMed and other search engines, and 2) an ancestry search by track-ing references cited in prior work. After screening the studies, we extracted information pertinent to the meta-analysis. We calculated the effect sizes for clinical pregnancy and live birth rates, and performed a moderation analysis by maternal age, type of genetic screening, and timing of the biopsy. For childhood outcomes, we conducted a systematic review of studies reporting the anthropometric, psychomotor, cognitive, behavioral, and family functioning of PGD/S children. Results We included 26 studies for clinical pregnancy and live births, and 18 studies for childhood outcomes. Results indi-cated that women who underwent comprehensive chromosome screening-based PGD/S had significantly higher clinical pregnancy rates (rr 1.207, 95% CI 1.017–1.431) and live birth rates (rr 1.362, 95% CI 1.057–1.755) than those whose IVF treatment did not include PGD/S. Early childhood outcomes of PGD/S children did not differ from those of non-PGD/S children. Conclusions Comprehensive chromosome screening-based PGD/S can improve clinical pregnancy and live birth rates without adversely affecting functioning in childhood at least up to age 9. Results are discussed in the context of bioethical, financial, legal, and psychological issues surrounding PGD/S.

Clinical relevance of salivary pepsin detection in diagnosing gastroesophageal reflux disease subtypes

Background:Gastroesophageal reflux disease(GERD)is heterogeneous with a varied symptom spectrum and reflux profiles.Its definite diagnosis often requires invasive tools including endoscopy or reflux monitoring.The aim of this study was to investigate the clinical relevance of salivary pepsin detection as a non-invasive screening tool to diagnose GERD of different subtypes.Methods:A total of 77 patients with suspected GERD symptoms and 12 asymptomatic controls were analysed.All participants performed symptom evaluation,upper endoscopy,esophageal manometry,and 24-hour multichannel intraluminal impedance-dual pH probe monitoring.Saliva was self-collected across three different time points:at early fasting,postprandially,and at symptom occurrence.Salivary pepsin levels were measured via Peptest.The optimal threshold of salivary pepsin for diagnosing distal or proximal reflux was determined according to a receiver-operating characteristic curve.Results:The average salivary pepsin concentration of suspected GERD patients was significantly higher than that of controls(100.63[68.46,141.38]vs 67.90[31.60,115.06]ng/mL,P=0.044),although no difference was found among patients with different symptom spectrums.The distal reflux group had a higher average pepsin concentration than non-reflux patients(170.54[106.31,262.76]vs 91.13[63.35,127.63]ng/mL,P=0.043),while no difference was observed between the distal reflux group and the proximal reflux group.The optimal cut-off value of salivary pepsin concentration for diagnosing pathological distal reflux was 157.10 ng/mL,which was higher than that for diagnosing pathological proximal reflux(122.65 ng/mL).The salivary pepsin concentration was significantly correlated with distal and proximal reflux parameters.Conclusions:Salivary pepsin measurement can help in identifying true GERD with pathological distal reflux or proximal reflux,regardless of different symptom spectrums.A higher threshold should be applied for diagnosing distal reflux than for proximal reflux.