Bowen-Conradi syndrome (BCS) is an autosomal-recessive disorder characterized by severely impaired prenatal and postnatal growth, profound psychomotor retardation, and death in early childhood. Nearly all reported BCS cases have been among Hutterites, with an estimated birth prevalence of 1/355. We previously localized the BCS gene to a 1.9 Mbp interval on human chromosome 12p13.3. The 59 genes in this interval were ranked as candidates for BCS, and 35 of these, including all of the best candidates, were sequenced. We identified variant NM_006331.6:c.400A-->G, p.D86G in the 18S ribosome assembly protein EMG1 as the probable cause of BCS. This mutation segregated with disease, was not found in 414 non-Hutterite alleles, and altered a highly conserved aspartic acid (D) residue. A structural model of human EMG1 suggested that the D86 residue formed a salt bridge with arginine 84 that would be disrupted by the glycine (G) substitution. EMG1 mRNA was detected in all human adult and fetal tissues tested. In BCS patient fibroblasts, EMG1 mRNA levels did not differ from those of normal cells, but EMG1 protein was dramatically reduced in comparison to that of normal controls. In mammalian cells, overexpression of EMG1 harboring the D86G mutation decreased the level of soluble EMG1 protein, and in yeast two-hybrid analysis, the D86G substitution increased interaction between EMG1 subunits. These findings suggested that the D-to-G mutation caused aggregation of EMG1, thereby reducing the level of the protein and causing BCS.

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Purpose of reviewMyocardial infarction with nonobstructive coronary artery disease (MINOCA) ( 50% stenosis) accounts for 5-8% of acute coronary syndrome (ACS) presentations. The demographic characteristics, risk factors, and management of patients with MINOCA differ from those with atherosclerotic ACS. The objective of this review is to provide a contemporary understanding of the epidemiology, pathophysiology, clinical presentation, and management of MINOCA. Recent findingsMINOCA is increasingly being recognized as an important and distinct cause of myocardial infarction among patients presenting with ACS. The predominant pathophysiologic mechanisms of MINOCA include both coronary (epicardial vasospasm, coronary microvascular disorder, spontaneous coronary artery dissection, coronary thrombus/embolism) and noncoronary (Takotsubo cardiomyopathy, myocarditis) pathologies. Coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offers important investigative modalities to facilitate diagnosis for appropriate management of MINOCA patients. SummaryMINOCA is an important cause of ACS observed in certain patients with unique challenges for diagnosis and management. A high index of suspicion and a comprehensive diagnostic evaluation are critical for early recognition and successful management.

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