Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance

Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES

Exome Sequencing in Neonates: Diagnostic Rates, Characteristics, and Time to Diagnosis.

Neonatal patients are particularly appropriate for utilization of diagnostic exome sequencing (DES), as many Mendelian diseases are known to present in this period of life but often with complex, heterogeneous features. We attempted to determine the diagnostic rates and features of neonatal patients undergoing DES.MethodsThe clinical histories and results of 66 neonatal patients undergoing DES were retrospectively reviewed.ResultsClinical DES identified potentially relevant findings in 25 patients (37.9%). The majority of patients had structural anomalies such as birth defects, dysmorphic features, cardiac, craniofacial, and skeletal defects. The average time for clinical rapid testing was 8 days.ConclusionOur observations demonstrate the utility of family-based exome sequencing in neonatal patients, including familial cosegregation analysis and comprehensive medical revie

Facing the Challenge of Genetic Counselors\u27 Need for Rapid Continuing Education About Genomic Technologies

The last couple of decades have seen the rapid advancement of genomic technologies (GT) and their equally rapid adoption into clinical testing. Regardless of specialty, all genetic counselors are unified by the fundamental goal to aid in diagnosing patient\u27s genetic disease underscoring the importance for genetic counselors to maintain an in-depth understanding of GT. The National Society of Genetic Counselors’ (NSGC) GT Special Interest Group conducted an online survey of NSGC members to assess current genomic technologies knowledge gaps. A total of 171 individuals from a variety of primary work settings completed the survey sufficiently to be included in the analysis. The majority of respondents received their degree in genetic counseling in more recent years (2000–2015). On average across all technologies, \u3e70% of respondents deemed knowledge of GTs as important for successful job performance, 55% responded that additional job training in GTs is needed to successfully perform job functions, and only 28% responded that graduate training in GTs was good. Overall, the data show that participating genetic counselors perceive that their knowledge of GTs is inadequate while it is a key component of their jobs. These results have implications both for training programs and for continuing education efforts. These data can be used as a starting point for additional research into GT educational needs of genetic counselors

When moments matter: Finding answers with rapid exome sequencing

Abstract Background When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing. Methods The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed. Results Clinical rapid exome sequencing identified a definitive diagnosis in 13/41 (31.7%) and other relevant findings in 17 of the patients (41.5%). The average time to verbal report was 7 days; to written report was 11 days. Conclusions Our observations demonstrate the utility and effectiveness of rapid family‐based diagnostic exome sequencing in improving patients care