De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.

Hexokinase 1 (HK1) phosphorylates glucose to glucose-6-phosphate, the first rate-limiting step in glycolysis. Homozygous and heterozygous variants in HK1 have been shown to cause autosomal recessive non-spherocytic hemolytic anemia, autosomal recessive Russe type hereditary motor and sensory neuropathy, and autosomal dominant retinitis pigmentosa (adRP). We report seven patients from six unrelated families with a neurodevelopmental disorder associated with developmental delay, intellectual disability, structural brain abnormality, and visual impairments in whom we identified four novel, de novo missense variants in the N-terminal half of HK1. Hexokinase activity in red blood cells of two patients was normal, suggesting that the disease mechanism is not due to loss of hexokinase enzymatic activity.

Implementation of a multidisciplinary pharmacogenomics clinic in a community health system.

PURPOSE: The development and implementation of a multidisciplinary pharmacogenomics clinic within the framework of an established community-based medical genetics program are described. SUMMARY: Pharmacogenomics is an important component of precision medicine that holds considerable promise for pharmacotherapy optimization. As part of the development of a health system-wide integrated pharmacogenomics program, in early 2015 Northshore University Health-System established a pharmacogenomics clinic run by a multidisciplinary team including a medical geneticist, a pharmacist, a nurse practitioner, and genetic counselors. The team identified five key program elements: (1) a billable-service provider, (2) a process for documentation of relevant medication and family histories, (3) personnel with the knowledge required to interpret pharmacogenomic results, (4) personnel to discuss risks, benefits, and limitations of pharmacogenomic testing, and (5) a mechanism for reporting results. The most important program component is expert interpretation of genetic test results to provide clinically useful information; pharmacists are well positioned to provide that expertise. At the Northshore University HealthSystem pharmacogenomics clinic, patient encounters typically entail two one-hour visits and follow a standardized workflow. At the first visit, pharmacogenomics-focused medication and family histories are obtained, risks and benefits of genetic testing are explained, and a test sample is collected; at the second visit, test results are provided along with evidence-based pharmacotherapy recommendations. CONCLUSION: A multidisciplinary clinic providing genotyping and related services can facilitate the integration of pharmacogenomics into clinical care and meet the needs of early adopters of precision medicine.