A Multidisciplinary Approach to Navigating Variants of Uncertain Significance in Sudden Infant Deaths: A Case Report of 2 Siblings With an SCN10A VUS.

The sudden death of a previously healthy infant is a devastating event for a family-the death of 2 even more unimaginable. Prior to the debunking of Meadow's law, a legal concept attributing multiple unexplained infant deaths to Munchausen by proxy, these events could lead to the wrongful prosecution of those who had lost their children to "sudden unexpected infant death (SUID)." Today, these cases, wherein multiple infants within one family pass inexplicably, raise suspicion for a possible genetic cause and point toward a need for postmortem genetic testing.

Biochemical signatures of disease severity in multiple sulfatase deficiency.

Sulfatases catalyze essential cellular reactions, including degradation of glycosaminoglycans (GAGs). All sulfatases are post-translationally activated by the formylglycine generating enzyme (FGE) which is deficient in multiple sulfatase deficiency (MSD), a neurodegenerative lysosomal storage disease. Historically, patients were presumed to be deficient of all sulfatase activities; however, a more nuanced relationship is emerging.

Surveying the Genomic Landscape Supporting the Development of Precision Military Aerospace Medicine.

Precision medicine is an approach to healthcare that is modifying clinical management by leveraging technological advances in genomics that assess a patient's genetic information to identify unique predispositions. While the civilian sector is integrating genomics widely to personalize diagnosis and treatment, the military medical environment has reacted more slowly. The operational requirements of military service encourage a tailored approach for focusing military precision medicine on occupation-specific conditions.

Precision Medicine-A Demand Signal for Genomics Education.

Pressed by the accumulating knowledge in genomics and the proven success of the translation of cancer genomics to clinical practice in oncology, the Obama administration unveiled a $215 million commitment for the Precision Medicine Initiative (PMI) in 2016, a pioneering research effort to improve health and treat disease using a new model of patient-powered research. The objectives of the initiative include more effective treatments for cancer and other diseases, creation of a voluntary national research cohort, adherence to privacy protections for maintaining data sharing and use, modernization of the regulatory framework, and forging public-private partnerships to facilitate these objectives. Specifically, the DoD Military Health System joined other agencies to execute a comprehensive effort for PMI.

Airmen and health-care providers' attitudes toward the use of genomic sequencing in the US Air Force: findings from the MilSeq Project.

Purpose: The use of genomic sequencing (GS) in military settings poses unique considerations, including the potential for GS to impact service members' careers. The MilSeq Project investigated the use of GS in clinical care of active duty Airmen in the United States Air Force (USAF).

Methods: We assessed perceived risks, benefits, and attitudes toward use of GS in the USAF among patient participants (n = 93) and health-care provider participants (HCPs) (n = 12) prior to receiving or disclosing GS results.

Educating military primary health-care providers in genomic medicine: lessons learned from the MilSeq Project.

Purpose: With few trained genetics professionals, the Military Health System is ill-equipped to manage the rapid expansion of genomic medicine. The MilSeq Project introduces an alternative service delivery model (ASDM) in which primary health-care providers (HCPs) provide post-test counseling (PTC) to healthy Airmen who have undergone exome sequencing. We describe HCP performance after a prerequisite educational intervention (EI).

Automated typing of red blood cell and platelet antigens from whole exome sequences.

Background: Genotyping has expanded the number red blood cell (RBC) and platelet (PLT) antigens that can readily be typed, but often represents an additional testing cost. The analysis of existing genomic data offers a cost-effective approach. We recently developed automated software (bloodTyper) for determination of RBC and PLT antigens from whole genome sequencing.

Return of secondary findings in genomic sequencing: Military implications.

Background: Genomic sequencing has become a widely used tool in clinical and research settings in both civilian and military healthcare systems.

Methods: In this paper, we consider potential military-specific implications of returning genomic sequencing secondary findings to ensure the proper protections, policies, and processes are in place for the use of this information.

Results: We specifically use two examples to highlight potential military implications of the return of secondary findings.

Correction to: Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins.

Unfortunately the name of one of the authors was spelled incorrectly in the published original article. The correct name is Alejandro Santos-Lozano. The original article got updated.

Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins.

McArdle disease is an autosomal recessive condition caused by deficiency of the PYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of "manifesting" heterozygotes or carriers (i.e.

Mandibular canal branching assessed with cone beam computed tomography.

Purpose: The mandibular canal must be considered in dental procedures to avoid injuries of the alveolar inferior nerve. The occurrence of anatomical variations of the mandibular canal increases the risk of neurovascular injuries. The purpose of this study was to identify and describe the prevalence of mandibular canal branching (MCB) using cone beam computer tomography (CBCT).

Complex care of individuals with multiple sulfatase deficiency: Clinical cases and consensus statement.

Multiple sulfatase deficiency (MSD) is an ultra-rare neurodegenerative disorder that results in defective sulfatase post-translational modification. Sulfatases in the body are activated by a unique protein, formylglycine-generating enzyme (FGE) that is encoded by SUMF1. When FGE is absent or insufficient, all 17 known human sulfatases are affected, including the enzymes associated with metachromatic leukodystrophy (MLD), several mucopolysaccharidoses (MPS II, IIIA, IIID, IVA, VI), chondrodysplasia punctata, and X-linked ichthyosis.

Military genomics: a perspective on the successes and challenges of genomic medicine in the Armed Services.

We describe the impact genomics has on the health and readiness of the military service member, highlight several examples of the current and future plans for genomic medicine within the military, discuss challenges to implementation and provide recommendations to address some of those challenges.

Johann Gregor Mendel: paragon of experimental science.

This is a foreword on the life and work of one of the greatest minds of the 20th century, the father of modern genetics, Johann Gregor Mendel.

Genomic medicine in the military.

The announcement of the Precision Medicine Initiative was an important step towards establishing the use of genomic information as part of the wider practice of medicine. The US military has been exploring the role that genomic information will have in health care for service members (SMs) and its integration into the continuum of military medicine. An important part of the process is establishing robust protections to protect SMs from genetic discrimination in the era of exome/genome sequencing.

Determining the prevalence of McArdle disease from gene frequency by analysis of next-generation sequencing data.

Purpose: McArdle disease is one of the most common glycogen storage disorders. Although the exact prevalence is not known, it has been estimated to be 1 in 100,000 patients in the United States. More than 100 mutations in PYGM have been associated with this disorder.

Severe neonatal holocarboxylase synthetase deficiency in west african siblings.

In multiple carboxylase deficiency (MCD), the biotin-dependent carboxylases have decreased activity due to either biotinidase deficiency or holocarboxylase synthetase (HS) deficiency. We report the case of two siblings from Ghana, the first of which presented shortly after birth with profound lactic acidosis and a urine organic acid profile consistent with MCD. In the first sibling, treatment with pulverized biotin tablets (20 mg) was begun immediately, but the patient died at 10 days of age from cardiac arrest secondary to refractory metabolic acidosis.