It’s all in their eyes: a three-generation family with branchio-oculo-facial syndrome (BOFS) reveals a heterozygous novel mutation in TFAP2A gene.

Introduction: Ocular defects are important semiological clues for the internist, leading sometimes to diagnose a familial disease. Branchio-oculo-facial syndrome is a rare congenital disorder characterized by ophtalmic malformations, branchial skin defects and craniofacial anomalies. Ocular features include coloboma of choroid and/or iris, microphtalmia, cataract, ptosis and strabismus. We herein describe a new three-generation family with BOFS. Patients The proband (A) was the 67 years-old grandfather. He presented with a left eye coloboma and microcornea. His only 39 years-old son (B) was diagnosed as a baby with a left coloboma and microphtalmia, right pre axial polydactilia. As an adult, B had a craniopharyngioma treated with surgery and radiotherapy. The 6 years-old grand daughter (C) had a left coloboma and microphtalmia and a right kidney hydrophrosis. The sister D of the proband presented a branchial fistula and a melanoma and his son (E) had a prolactinoma. Because of this intriguing phenotype, an inherited anomaly closest to BOFS was suspected in this non consanguineous family. Genetic Studies In 2011, BMP4 gene study was unremarkable. In 2018 none PAX2 (coloboma-kidney sundrome) nor PAX6 gene mutation were found, among a panel of different 35 genes. Then, a panel of ocular developmental genetic anomalies was done in this family. Finally, a large MAC-ASD genetic panel found only in A, B and C patients an heterozygous frameshift variant in exon 2/7 of the TFAP2 gene: c.38-56 dup, p.(Ala20ArgfsTer149). This is a likely pathogenic variant (type IV), causing a mutation stop codon in exon 2 in transcription factor AP2-alpha gene (TFAP2A). Discussion TFAP2A mutations have been related with BOFS, ectopic thymus and anophthalmia-microphthalmia syndrome. Reported BOFS associated malformation are diverse and heterogeneous, like in most dominant diseases. We report a novel TFAP2A mutation in a three-generational BOFS affected family. TFAP2A is a retinoic acid response gene to direct ocular morphogenesis. It is localized on the minus strand of chromosome 6. In addition, two antisense non-coding RNA molecules have been identified. TFAP2A also regulates gene expression during embryogenesis of the eye, ear, face, body wall, limbs, kidney and neural tube in humans as well as in Tfap2 knockout mice embryos. A, B and C presented with coloboma whereas B had also right pre axial polydactilia. We thought to also study B and D for a TFAP2A mutation, because there is a down-regulation of AP-2α in some tumors (like hepatic carcinoma), with has an impact on Wnt/β-catenin pathway (like in craniopharyngiomas), and there is abolition of TFAP2A expression in melanoma. Intriguingly, D did not have the familial TFAP2 mutation although she had a melanoma and branchial fistula. Moreover, the presence of two unrelated pituitary tumors in B and E remain unexplained. TFAP2A mosaicism could not been excluded

Pre-study and in-study validation of an ultra-high pressure LC method coupled to tandem mass spectrometry for off-line determination of oxytetracycline in nasal secretions of healthy pigs.

In order to quantify oxytetracycline (OTC) in nasal secretions of healthy pigs after intramuscular injection of OTC at doses of 10, 20 and 40 mg/kg bodyweight, an original method based on ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was developed and fully validated. Sample preparation consisted in protein precipitation preceded by the addition of a releasing protein reagent. Metacycline (MTC) was used as internal standard. Separation was carried out at 65 degrees C in the gradient elution mode on a short analytical column filled with Acquity BEH C(18) stationary phase. The mobile phase consisted in a mixture of water and acetonitrile containing 1 mM of oxalic acid and 0.1% (v/v) of formic acid. The triple quadrupole mass spectrometer operated in the positive electrospray ionization mode; OTC and MTC were detected using multiple reaction monitoring. The pre-study and in-study validation of this bioanalytical method was performed by applying a novel strategy based on total measurement error and accuracy profiles. The maximum risk of observing future measurements falling outside the acceptance limits during routine as well as the measurements uncertainty were also estimated

Prophylaxis of postoperative endophthalmitis following cataract surgery: Results of the ESCRS multicenter study and identification of risk factors

Purpose: To identify risk factors and describe the effects of antibiotic prophylaxis on the incidence of postoperative endophthalmitis after cataract surgery based on analysis of the findings of the European Society of Cataract & Refractive Surgeons (ESCRS) multicenter study. Setting: Twenty-four ophthalmology units in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom. Methods: A prospective randomized partially masked multicenter cataract surgery study recruited 16 603 patients. The study was based on a 2 × 2 factorial design, with intracameral cefuroxime and topical perioperative levofloxacin factors resulting in 4 treatment groups. The comparison of case and non-case data was performed using multivariable logistic regression analyses. Odds ratios (ORs) associated with treatment effects and other risk factors were estimated. Results: Twenty-nine patients presented with endophthalmitis, of whom 20 were classified as having proven infective endophthalmitis. The absence of an intracameral cefuroxime prophylactic regimen at 1 mg in 0.1 mL normal saline was associated with a 4.92-fold increase (95% confidence interval [CI], 1.87-12.9) in the risk for total postoperative endophthalmitis. In addition, the use of clear corneal incisions (CCIs) compared to scleral tunnels was associated with a 5.88-fold increase (95% CI, 1.34-25.9) in risk and the use of silicone intraocular lens (IOL) optic material compared to acrylic with a 3.13-fold increase (95% CI, 1.47-6.67). The presence of surgical complications increased the risk for total endophthalmitis 4.95-fold (95% CI, 1.68-14.6), and more experienced surgeons were more likely to be associated with endophthalmitis cases. When considering only proven infective endophthalmitis cases, the absence of cefuroxime and the use of silicone IOL optic material were significantly associated with an increased risk, and there was evidence that men were more predisposed to infection (OR, 2.70; 95% CI, 1.07-6.8). Conclusions: Use of intracameral cefuroxime at the end of surgery reduced the occurrence of postoperative endophthalmitis. Additional risk factors associated with endophthalmitis after cataract surgery included CCIs and the use of silicone IOLs. © 2007 ASCRS and ESCRS