Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Associations between dietary mycotoxins exposures and risk of hepatocellular carcinoma in a European cohort

Mycotoxins have been hypothesized to contribute to a diversity of adverse health effects in humans, even at low concentrations. Certain mycotoxins are established human carcinogens, whereas for others research suggests potential carcinogenic effects. The aim of this study was to determine the association between dietary exposure to mycotoxins and hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. EPIC questionnaire data were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority to assess long-term dietary mycotoxin exposure (expressed as mu g/kg body weight/day) and then relate them to the risk of hepatocellular carcinoma (HCC) (n = 255) and biliary tract cancers (n = 273). Analyses were conducted using multivariable Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (95% CI). Key food groups contributing to mycotoxin exposure were cereals and cereal-based products, vegetables, non-alcoholic beverages (including fruit juices) and fruits. Estimated intake of deoxynivalenol (DON) and its derivatives was positively associated with HCC risk (HRT3vsT1: 1.90, 95% CI: 1.18-3.05, p-trend <0.01). No statistically significant associations were found for the other mycotoxins. Further research to confirm our observations and investigate potential underlying mechanisms of these compounds is warranted. These data may provide evidence of HCC risks associated with higher dietary intake levels of DON, which has not yet been classified as a human carcinogen

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability