Cranio-lenticulo-sutural dysplasia (CLSD) is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects mapped to chromosome 14q13-q21 (ref. 1). Here we show, using a positional cloning approach, that an F382L amino acid substitution in SEC23A segregates with this syndrome. SEC23A is an essential component of the COPII-coated vesicles that transport secretory proteins from the endoplasmic reticulum to the Golgi complex. Electron microscopy and immunofluorescence show that there is gross dilatation of the endoplasmic reticulum in fibroblasts from individuals affected with CLSD. These cells also exhibit cytoplasmic mislocalization of SEC31. Cell-free vesicle budding assays show that the F382L substitution results in loss of SEC23A function. A phenotype reminiscent of CLSD is observed in zebrafish embryos injected with sec23a-blocking morpholinos. Our observations suggest that disrupted endoplasmic reticulum export of the secretory proteins required for normal morphogenesis accounts for CLSD.

Keutel syndrome (KS) [OMIM 245150] is a rare autosomal recessive condition, characterized by abnormal cartilage calcification. Mutations in the matrix Gla protein gene (MGP) have been previously reported in three unrelated KS families. MGP is an extracellular matrix protein that acts as a calcification inhibitor by repressing bone morphogenetic protein 2 (BMP2). Loss-of-function mutations of MGP result in abnormal calcification of the soft tissues, a cardinal feature of KS. We report the fourth MGP mutation (IVS2 + 1G > A) in a consanguineous Arab family, which results in the loss of the consensus donor splice site at the exon 2-intron 2 junction. In addition to the typical manifestations, we observed abnormalities in the white matter of the brain, optic nerve atrophy, and mid-dermal elastolysis in the affected individuals of this family. This report broadens the clinical phenotype observed in patients with KS. The effect of the IVS2 + 1G > A mutation is consistent with the previously reported loss-of-function mutations of MGP.

The prevalence of coronary artery disease (CAD) in patients with peripheral arterial disease (PAD) varies widely in published reports. This is likely due, at least in part, to significant differences in how PAD and CAD were both defined and diagnosed. We describe 78 patients with PAD who underwent pre-operative coronary angiography prior to elective peripheral revascularization and provide a review of published case series. In our patients the number with concomitant CAD varied from 55% in those with lower extremity stenoses to as high as 80% in those with carotid artery disease. The number of coronary arteries narrowed by ≥50% in our patients was 1 in 28%, 2 in 24% and 3 in 19%; 28% did not have any angiographic evidence of CAD. Our review of the literature resulted in identification of 19 case series in which a total of 3969 patients underwent pre-operative coronary angiography prior to elective PAD surgery; in the 2687 that were described according to the location of the PAD, 55% had at least one epicardial coronary artery with ≥70% diameter narrowing. The highest prevalence of concomitant CAD was in patients with severe carotid artery disease (64%). In conclusion, despite sharing similar risk factors the prevalence of obstructive CAD in patients with PAD ranges widely, and appears to differ across PAD locations. Thus, the decision to perform coronary angiography should be based on indications independent of the planned PAD surgery.

Heavy snowfall, cold temperatures, and low atmospheric pressure during the winter months have been associated with increased adverse cardiovascular events. However, only a few cases of the “snow -shoveler’s infarction ” have been reported. We present our experience with 6 patients presenting with ST elevation myocardial infarction all within a 24-hour period during an unprecedented snowfall (4 of whom were shoveling snow), and provide a detailed review of previously reported cases of snow-shoveler’s infarction. Consistent with other reports, the majority of our patients had the traditional cardiac risk factors of hypertension, hyperlipidemia, diabetes mellitus, tobacco use, and were habitually sedentary. Unique to our case series, however, was that the four patients who had a history of coronary artery disease and prior coronary artery stenting, all presented with subacute stent thrombosis documented on the coronary angiography performed emergently. Moreover, these patients constituted 25% of all the subacute stent thromboses diagnosed in our cardiac catheterization laboratory over the preceding 12 months. In conclusion, our findings suggest that in typically sedentary individuals with cardiac risk factors or a history of coronary artery disease, snow shoveling may trigger ST elevation myocardial infarction and, therefore, should be avoided. This may be most critical in patients with a history of coronary stent placement since our findings suggest that snow shoveling may precipitate subacute stent thrombosis.