Characterizing a rare neurogenetic disease, SLC13A5 citrate transporter disorder, utilizing clinical data in a cloud-based medical record collection system.

SLC13A5 citrate transporter disorder is a rare autosomal recessive genetic disease that has a constellation of neurologic symptoms. To better characterize the neurologic and clinical laboratory phenotype, we utilized patient medical records collected by Ciitizen, an Invitae company, with support from the TESS Research Foundation. Medical records for 15 patients with a suspected genetic and clinical diagnosis of SLC13A5 citrate transporter disorder were collected by Ciitizen, an Invitae company.

Clinician-Reported Impact of Germline Multigene Panel Testing on Cancer Risk Management Recommendations.

Background: With increased adoption of multi-gene panel testing (MGPT) for hereditary cancer, management guidelines now include a wider range of predisposition genes. Yet little is known about whether MGPT results prompt changes to clinicians' risk management recommendations and whether those recommendations adhere to guidelines.

Methods: We assessed cancer risk management recommendations made by clinicians ordering MGPT for hereditary cancer at a diagnostic laboratory using an internet-based survey.

Misattributed parentage identified through diagnostic exome sequencing: Frequency of detection and reporting practices.

Access to genetic testing, namely, diagnostic exome sequencing (DES), has significantly improved, subsequently increasing the likelihood of discovering incidental findings, such as misattributed relationships and specifically misattributed parentage (MP). Until the recently published ACMG statement, there had been no consensus for laboratories and clinicians to follow when addressing such findings. Family-based genomic testing is valuable for accurate variant interpretation but has the potential to uncover misattributed familial relationships.

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies.

When moments matter: Finding answers with rapid exome sequencing.

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.

Clinical diagnostic exome sequencing in dystonia: Genetic testing challenges for complex conditions.

Patients with dystonia are particularly appropriate for diagnostic exome sequencing (DES), due to the complex, diverse features and genetic heterogeneity. Personal and family history data were collected from test requisition forms and medical records from 189 patients with reported dystonia and available family members received for clinical DES. Of them, 20.

A retrospective review of multiple findings in diagnostic exome sequencing: half are distinct and half are overlapping diagnoses.

Purpose: We evaluated clinical and genetic features enriched in patients with multiple Mendelian conditions to determine which patients are more likely to have multiple potentially relevant genetic findings (MPRF).

Methods: Results of the first 7698 patients who underwent exome sequencing at Ambry Genetics were reviewed. Clinical and genetic features were examined and degree of phenotypic overlap between the genetic diagnoses was evaluated.

Exome sequencing in neonates: diagnostic rates, characteristics, and time to diagnosis.

Purpose: 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.

Methods: The clinical histories and results of 66 neonatal patients undergoing DES were retrospectively reviewed.

Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects.