Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.

Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels

Should antibiotic prophylaxis before orthopedic implant surgery depend on the duration of pre-surgical hospital stay?

Abstract Background Prolonged hospital stay before surgery is a risk for colonization with antibiotic-resistant microorganisms and possible antibiotic-resistant surgical site infections (SSI), which lacks acknowledgement in international guidelines for perioperative antibiotic prophylaxis. Method Retrospective cohort study focusing on prophylaxis-resistant SSI in adult orthopedic implant patients; with emphasis on length of hospital stay prior to the index surgery. Results We enrolled 611 cases of SSI (median age, 65 years; 241 females and 161 immune-suppressed) in four large implant groups: arthroplasties (n = 309), plates (n = 127), spondylodeses (n = 31), and nails (n = 46). The causative pathogen was resistant to the perioperative antibiotic prophylaxis regimen in 307 cases (307/611; 50%), but the length of pre-surgical hospitalization did not influence the incidences of prophylaxis-resistant SSIs. These incidences were (107/211;51%) for the admission day, (170/345;49%) within 10 days of delay, (19/35;54%) between 10 and 20 days, and (11/20; 55%) beyond 20 days of hospital stay before surgery. The corresponding incidences of methicillin-resistant staphylococci were 13%, 14%, 17%, and 5%, respectively. In adjusted group comparisons, the length of prior hospital stay was equally unrelated to future prophylaxis-resistant SSI (odds ratio 1.0, 95% confidence interval 0.99–1.01). Conclusions In our retrospective cohort of orthopedic implant SSI, the length of pre-surgical hospital stay was unrelated to the incidence of prophylaxis-resistant pathogens