Genotype - phenotype Study of Patients with Plaquenil^-induced Retinal Toxicity,

吡喹尼或羟基氯喹及其相关化合物氯喹，长期以来被认为与视网膜毒性有关。这种毒性很少发生（在药物患者的0.5-3.5%范围内），但是，尽管如此，它仍然令人担忧，因为对视网膜的毒性大部分（如果不是完全的话）是不可逆的，并且这种毒性的视觉后遗症可能是毁灭性的。ABCA4基因突变与Plaquenil毒性的发生之间存在一定的关系。如果ABCA4突变或其他基因突变与Plaquenil毒性之间的关系被确定，这将使个性化医疗的实践成为可能。个性化医疗的实践得到了美国国会的一项法案的支持，并利用基因测序获得的知识来定制个人医疗保健。因此，考虑使用羟氯喹或氯喹治疗的患者应进行基因突变（如ABCA4突变）的遗传筛查，以便在实施治疗之前确定对该药物毒性作用非常敏感的患者。

Plaquenil, or hydroxychloroquine, and its related compound chloroquine, has long been identified to be associated with a retinal toxicity. This toxicity occurs rarely (in the range of 0.5-3.5% of patients on the drug), but, nevertheless, it remains a concern as the toxicity to the retina is mostly, if not wholly, irreversible and the visual sequelae from this toxicity can be devastating. A relationship has been proposed between mutations in the ABCA4 gene and the development of Plaquenil toxicity. If a relationship between ABCA4 mutations, or other genetic mutations, and Plaquenil toxicity is identified this would enable the practice of personalized medicine. The practice of personalized medicine is supported by a bill from the US congress and utilizes the knowledge gained by genetic sequencing to tailor an individuals medical care. It would follow that patients considered for hydroxychloroquine or chloroquine therapy undergo genetic screening for genetic mutations, such as ABCA4 mutations, so that patients who would be exquisitely sensitive to toxic effects of this drug are identified before the treatment is implemented. The objective of this study is to identify genetic mutations, starting with an analysis of ABCA4 mutations, that may be correlated with Plaquenil toxicity and correlate these with the participants phenotypes. This study will recruit 30 patients with Plaquenil-induced retinal toxicity and at least 60 control participants to participate in this study. This is an observational study that requires 1-2 outpatient visits to the NIH Clinical Center or a local ophthalmologists office over a period of time convenient to the participants, not to exceed two years. After gathering a complete medical, family and surgical history, participants will have standard physical and eye examination. The eye examination will include a dilated fundus examination. Non-invasive ophthalmologic testing (e.g., visual field testing, OCT, photos, and autofluorescence) may be performed. Photographs (ophthalmic) will be taken to document the Plaquenil toxicity. Participants will have a 30 cc blood sample drawn for genetic analysis. During this fiscal year, the protocol has gained IRB-approval and recruitment of patients has started. An electronic medical record form has been developed and utilized to store clinical data collected as part of this protocol. The collaboration with Dr. Ayyagaris lab at University of California San Diego will provide the expertise in sequencing and determining the significance of any mutations detected in the patients DNA samples. We have enrolled participants and continue to enroll participants into this study at the NEI.