Views on increased federal access to state and local National Syndromic Surveillance Program data: a nominal group technique study with state and local epidemiologists.

BACKGROUND: US public health authorities use syndromic surveillance to monitor and detect public health threats, conditions, and trends in near real-time. Nearly all US jurisdictions that conduct syndromic surveillance send their data to the National Syndromic Surveillance Program (NSSP), operated by the US. Centers for Disease Control and Prevention. However, current data sharing agreements limit federal access to state and local NSSP data to only multi-state regional aggregations. This limitation was a significant challenge for the national response to COVID-19. This study seeks to understand state and local epidemiologists' views on increased federal access to state NSSP data and identify policy opportunities for public health data modernization. METHODS: In September 2021, we used a virtual, modified nominal group technique with twenty regionally diverse epidemiologists in leadership positions and three individuals representing national public health organizations. Participants individually generated ideas on benefits, concerns, and policy opportunities relating to increased federal access to state and local NSSP data. In small groups, participants clarified and grouped the ideas into broader themes with the assistance of the research team. An web-based survey was used to evaluate and rank the themes using five-point Likert importance questions, top-3 ranking questions, and open-ended response questions. RESULTS: Participants identified five benefit themes for increased federal access to jurisdictional NSSP data, with the most important being improved cross-jurisdiction collaboration (mean Likert = 4.53) and surveillance practice (4.07). Participants identified nine concern themes, with the most important concerns being federal actors using jurisdictional data without notice (4.60) and misinterpretation of data (4.53). Participants identified eleven policy opportunities, with the most important being involving state and local partners in analysis (4.93) and developing communication protocols (4.53). CONCLUSION: These findings identify barriers and opportunities to federal-state-local collaboration critical to current data modernization efforts. Syndromic surveillance considerations warrant data-sharing caution. However, identified policy opportunities share congruence with existing legal agreements, suggesting that syndromic partners are closer to agreement than they might realize. Moreover, several policy opportunities (i.e., including state and local partners in data analysis and developing communication protocols) received consensus support and provide a promising path forward.

A case of G1013R FBN1 mutation: A potential genotype-phenotype correlation in severe Marfan syndrome.

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder with a wide range of severities. Ninety-five percent of MFS probands have a mutation in the fibrillin-1 gene (FBN1); however, there are a high number of unique mutations complicating attempts at establishing any phenotype-genotype correlations for this disease (Tiecke et al., European Journal of Human Genetics, 2001, 9, 13-21). One of the few extant genotype-phenotype correlations is in exon 24-32 which have been associated with a severe pediatric presentation of neonatal MFS with predominately cardiovascular symptoms. We present a 24-year-old male patient with a heterozygous de novo variant NM_000138.4: c.3037G>A (p.G1013R) located in exon 25 of the FBN1 gene. The patient was found to have dysplastic mitral and tricuspid valves with dilated aortic root at 9 months of age. This is a notable case in that the location of this patient's mutation and his age of symptom onset would indicate a guarded prognosis. Further, this mutation, FBN1 G1013R, has been reported in the literature in four other unrelated patients all of whom presented at a young age with cardiac involvement and all of whom had relative longevity when compared to other patients with mutations in this exon 24-32 hot spot. These findings may represent a more specific genotype-phenotype correlation within this mutational hot spot.

Primary coenzyme Q10 deficiency-7: expanded phenotypic spectrum and a founder mutation in southern Chinese.

Primary coenzyme Q10 deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.

Development of clinical genetics in Asia.

This Special Issue on Clinical Genetics in Asia highlights a collection of articles showing the growth, development, and current status of clinical genetics in Asia. In this Introduction, the Guest Editors share on the themes of this issue to provide useful insights into the rapid growth of genomics and clinical genetics in this region. The contents of this Issue cover a range of topics from the history and development of clinical genetics in Asia to studies on disorders with clinical significance or phenotype differences in the Asian populations to the status of precision medicine. The goal is to provide a glimpse of how significantly the field of genetics in Asia has developed in recent years with the aspiration that this can serve as a catalyst to increase international collaboration and cooperation in combating genetic diseases. We hope that this issue shows Asia's readiness and willingness to be a part of more international conversations about genetics in future.

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand-induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the binding of a nonhydrolyzable GTP analogue [(35)S]GTPγS binding to specific G protein subtypes in response to odorants, dopamine, or serotonin in ON cell membranes from matched schizophrenia-control subjects. In response to odorant mixtures, we found decreased [(35)S]GTPγS binding to Gαs/olf in schizophrenia patients. These changes were not mediated by mRNA expression of key molecules of G protein coupling, including adenylate cyclase III (ACIII), protein kinase A (PKA), protein kinase Cγ (PKCγ), or Gαs or Gαolf in ON cells or ON biopsy tissues. In contrast, dopamine (DA)- and serotonin (5HT)-induced S(35)-GTPγS binding to Gαs/olf and Gαq/11 were significantly increased in schizophrenia cases, while these parameters were strikingly reduced by in vitro treatment with antipsychotics. Patients with schizophrenia exhibit increases in electrolfactogram (EOG) recordings, suggesting enhanced odorant-induced activation. Our results of decreased odorant-induced G protein activation may point further downstream for underlying mechanisms for increased EOG measures. Increased G protein activation in response to DA and 5HT may suggest increased postreceptor DA or 5HT signaling as an additional mechanism of dopaminergic or serotonergic dysregulation in schizophrenia.