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SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a patient compound heterozygous for the p.(Trp284Ser) and a novel splice site change (c.997-1G > T). Clinical severity ranged from prenatal onset with severe features at birth, to a milder and slowly progressive congenital myopathy phenotype. A malignant hyperthermia (MH)-like reaction had occurred in several patients. The functional analysis demonstrated impaired ECC. In particular, KCl-induced membrane depolarization resulted in significantly reduced sarcoplasmic reticulum Ca2+ release. Co-immunoprecipitation of STAC3 with CaV 1.1 in patients and control muscle samples showed that the protein interaction between STAC3 and CaV 1.1 was not significantly affected by the STAC3 variants. This study demonstrates that STAC3 gene analysis should be included in the diagnostic work up of patients of any ethnicity presenting with congenital myopathy, in particular if a history of MH-like episodes is reported. While the precise pathomechanism remains to be elucidated, our functional characterization of STAC3 variants revealed that defective ECC is not a result of CaV 1.1 sarcolemma mislocalization or impaired STAC3-CaV 1.1 interaction.

Perioperative mortality has fallen in both high- and low-income countries over the last 50 years. An evaluation of avoidable perioperative mortality can provide valuable lessons to improve care; however, there is relatively little recent data from the Least Developed Countries in the world. We aimed to compare recent avoidable perioperative mortality in Lusaka, Zambia, with historical data from 1987. We conducted a retrospective cohort study by identifying perioperative deaths within days of surgery and comparing the operating room and mortuary registers for the 2012 calendar year. Multiple independent raters from anesthesiology and surgery/obstetrics gynecology reviewed case notes, when available, to identify avoidable causes of death. Of the 18,010 surgical patients in 2012, 114 were identified as having died perioperatively within six days of surgery. Fifty-nine files were available for further analysis (52% of identified perioperative deaths). Eighteen (30%) of these cases were assessed as avoidable, 19 cases (32%) probably avoidable, 14 cases (24%) unavoidable, and eight cases (14%) unclear. Thirty-one (53%) cases had surgical factors contributing to death, 19 (32%) cases had anesthesia factors, and 18 (30%) cases had systems factors. Most of the avoidable deaths were attributed to multiple factors. Key factors leading to the avoidable deaths were delays in surgery, lack of the availability of blood, and poor postoperative care. Most deaths were avoidable, suggesting that patient outcomes in low-resource settings can be improved within current resources. The multifactorial nature of avoidability implies that an interprofessional approach is required to improve the quality of care.