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Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.

Current guideline recommendations for pharmacogenetic testing for clopidogrel by the American Heart Association/American College of Cardiology (AHA/ACC) contradict the Clinical Pharmacogenetics Implementation Consortium and the US FDA. The AHA/ACC recommends against routine pharmacogenetic testing for clopidogrel because no randomized controlled trials have demonstrated that testing improves patients' outcomes. However the AHA/ACC and the National Comprehensive Cancer Network (NCCN) recommend other pharmacogenetic tests in the absence of randomized controlled trials evidence. Using clopidogrel as a case example, we compared the evidence for other pharmacogenetic tests recommended by the AHA/ACC and NCCN. In patients that received percutaneous coronary intervention, the evidence supporting pharmacogenetic testing for clopidogrel is stronger than other pharmacogenetic tests recommended by the AHA/ACC and NCCN.