Pathogenic missense variants altering codon 336 of GARS1 lead to divergent dominant phenotypes.

Heterozygosity for missense variants and small in-frame deletions in GARS1 has been reported in patients with a range of genetic neuropathies including Charcot-Marie-Tooth disease type 2D (CMT2D), distal hereditary motor neuropathy type V (dHMN-V), and infantile spinal muscular atrophy (iSMA). We identified two unrelated patients who are each heterozygous for a previously unreported missense variant modifying amino-acid position 336 in the catalytic domain of GARS1. One patient was a 20-year-old woman with iSMA, and the second was a 41-year-old man with CMT2D. Functional studies using yeast complementation assays support a loss-of-function effect for both variants; however, this did not reveal variable effects that might explain the phenotypic differences. These cases expand the mutational spectrum of GARS1-related disorders and demonstrate phenotypic variability based on the specific substitution at a single residue.

Influence of family history of diabetes on health care provider practice and patient behavior among nondiabetic Oregonians.

INTRODUCTION: People with a family history of diabetes are at increased risk of developing diabetes; however, the effect of family history of diabetes on health care provider practice and patient behavior has not been well defined. METHODS: We analyzed data from the 2005 Oregon Behavioral Risk Factor Surveillance System, a state-based, random-digit-dialed telephone survey, to evaluate, among people with diabetes, associations between family history of diabetes and 1) patients' reports of health care provider practices, 2) patients' perceived risk of developing diabetes, and 3) patients' behaviors associated with an increased risk of developing diabetes. RESULTS: Compared with respondents at average risk, respondents with a positive family history (strong or moderate familial risk for diabetes) were more likely to report that their health care provider collects family history information about diabetes, discusses the risk of developing diabetes or other chronic conditions, and makes recommendations to change their diet or exercise behaviors to reduce the chance of developing diabetes. Respondents with a strong family history of diabetes were 5 times more likely to be very or somewhat worried about developing diabetes than were people at average risk (odds ratio [OR], 5.0; 95% confidence interval [CI], 4.0-6.2). Compared with respondents at average risk, respondents with a strong family history were more likely to report making changes in diet and exercise (OR, 1.7; 95% CI, 1.4-2.1). CONCLUSION: Integrating family history of diabetes into clinical practice offers opportunities to improve the effectiveness of diabetes detection and to promote interventions aimed at preventing or delaying the development of diabetes in people at high risk.

Public awareness and use of direct-to-consumer genetic tests: results from 3 state population-based surveys, 2006.

We conducted population-based surveys on direct-to-consumer nutrigenomic testing in Michigan, Oregon, and Utah as part of the 2006 Behavioral Risk Factor Surveillance System. Awareness of the tests was highest in Oregon (24.4%) and lowest in Michigan (7.6%). Predictors of awareness were more education, higher income, and increasing age, except among those 65 years or older. Less than 1% had used a health-related direct-to-consumer genetic test. Public health systems should increase consumer and provider education and continue surveillance on direct-to-consumer genetic tests.