 Hello, I'm Dr. Mike Nickerson. I'm corresponding author of a paper to be published in the journal Human Mutation, entitled the UBID-1 Prenyl Transferase Links Mediquinone Synthesis to Cholesterol Metabolic Enzymes. Snyder's Cornell Dystrophy was first identified in 1924 by two Dutch researchers, but takes its name after work by Walter Snyder of Switzerland based on papers published in 1929 and 1939. The phenotype of the disease is very striking and is shown in Figure 1 from the paper. The phenotype arises from abnormal deposition of cholesterol and lipids in patient corneas, resulting in decreased visual acuity and usually requiring a corneal transplant later in life. The photos in Figure 1 were taken by Dr. Jane Weiss, who identified her first SCD patients in the late 1980s at the University of Massachusetts Medical Center. Identification of those patients led to a 25-year effort by Dr. Weiss to collect framies from around the world, which would later enable identification of the disease gene. I began working with Dr. Weiss in late 2005 and we published our results identifying UBID-1 as mutated in SCD in 2007. A few weeks after a group from Canada led by Dr. Mark Samuels published identification of the same gene as mutated in SCD. The current work shows a novel mutation in six families with SCD, four of which are from a region of Finland within 60 kilometers of each other. The mutation is a G2A change, resulting in a substitution of glycine at 177 with a glutamic acid. We show that the mutation in the Swedish Finnish families is likely a founder mutation. The four different families share an identical haplotype across the UBID-1 locus, and the alteration cosegregated very nicely with disease in virtually all patients examined. We immediately were interested in the enzymatic implications of SCD mutations and working with Toshio Okano of Japan, who recently published in Nature that UBID-1 was the first vitamin K biosynthesis enzyme. We examined wild type and SCD mutant UBID-1 to find that vitamin K biosynthesis was reduced by 20% to 40% by different SCD mutations. We performed molecular modeling on SCD mutant UBID-1 with Dr. Wolfgang Brandt of Germany, and we show that the SCD mutation introduced striking structural perturbations to transmembrane helices and key amino acid residues in the active site. So molecular modeling results coincided very nicely with our enzymology results. We went on to show with Dr. Thorkel Anderson of SAIC in Frederick that UBID-1 bound to two enzymes that are key components of cholesterol synthesis and processing in cells. These are HMG-CoA reductase, which is a target of statins, and it is a key regulatory enzyme in cholesterol synthesis. And also, SOAT-1, a key enzyme in cholesterol storage. SOAT-1 asterifies cholesterol for storage within cells. In conclusion, we have a novel alteration in SWEED-FIN SCD families. We have now examined the global collection of SCD families, which totals 51 families, and we have found 23 different missense alterations. We think these results have implications for corneal health, vitamin K2 action in coagulation, and also vitamin K2 function in the electron transport chain in mitochondria. Enjoy reading the paper. Thank you very much and feel free to contact me with questions. Thank you.