Adult-onset dominant muscular dystrophy in Greek families caused by Annexin A11

Objective: Mutations in the prion-like domain of RNA binding proteins cause dysfunctional stress responses and associated aggregate pathology in patients with neurogenic and myopathic phenotypes. Recently, mutations in ANXA11 have been reported in patients with amyotrophic lateral sclerosis and multisystem proteinopathy. Here we studied families with an autosomal dominant muscle disease caused by ANXA11:c.118G > T;p.D40Y. Methods: We performed deep phenotyping and exome sequencing of patients from four large Greek families, including seven affected individuals with progressive muscle disease but no family history of multi-organ involvement or ALS. Results: In our study, all patients presented with an autosomal dominant muscular dystrophy without any Paget disease of bone nor signs of frontotemporal dementia or Parkinson's disease. Histopathological analysis showed rimmed vacuoles with annexin All accumulations. Electron microscopy analysis showed myofibrillar abnormalities with disorganization of the sarcomeric structure and Z-disc dissolution, and subsarcolemmal autophagic material with myeloid formations. Molecular genetic analysis revealed ANXA11:c.118G > T;p.D4OY segregating with the phenotype. Interpretation: Although the pathogenic mechanisms associated with p.D4OY mutation in the prion-like domain of Annexin All need to be further clarified, our study provides robust and clear genetic evidence to support the expansion of the phenotypic spectrum of ANXA11.Peer reviewe

Primary tooth abscess caused by Mycobacterium bovis in an immunocompetent child

Bovine tuberculosis is a zoonotic disease, and although its incidence has dramatically decreased in developed countries where effective control measures are applied, it still remains a potential health hazard in the developing world. Tuberculosis of the oral cavity is extremely rare and is usually secondary to pulmonary involvement. We present the unusual case of an immunocompetent 6-year-old child residing in an urban area with primary oral tuberculosis due to Mycobacterium bovis, which was confirmed by the application of a molecular genetic approach. M. bovis belongs to Mycobacterium tuberculosis complex which comprises species with close genetic relationship, and for this reason, the use of new molecular techniques is a useful tool for the differentiation at species level of the closely related members of this complex

Lipids, lipoproteins, apolipoproteins, selected trace elements and minerals in the serum of children on valproic acid monotherapy

We evaluated the serum levels of lipids, lipoproteins, apolipoproteins, along with a number of minerals and trace elements such as Ca, Mg, Cu and Zn in a group of children after 6 months of valproic acid monotherapy. Thirty patients with seizures, mean age, 9.8 +/- 2.6 years and 79 healthy children (controls), mean age, 10.9 +/- 3.2 years. formed the two styd groups. The patient group was treated with valproic acid (27.9 +/- 14.8 mg/kg/24 hr). Patients underwent clinical and laboratory evaluations including liver function tests. NH3, lipid, mineral and selected trace element levels before and after six months on valproic acid treatment, whereas controls only one evaluation. Liver function data and NH3 levels were found to be elevated in the group of patients. whereas albumin level was reduced. Triglycerides, total cholesterol, HDL-C, apolipoprotein (ApoA)-1, Apo B and Ca concentrations were found relative to control values. LDL-C, VLDL-C, Mg, Cu, Zn, were measured significantly altered (P < 0.0001) compared to controls. The ratios ApoA-1/ApoB, HDL-C/ApoA-1, LDL-C/Apo B, which were closely related to the size of LDL particles, where correlated with Zn/Cu (P < 0.001). Serum lipid profile, especially LDL size, indirectly evaluated for the first time and metal levels were found to be significantly changed, after six months on valproic acid monotherapy, suggesting a possible risk of developing coronary heart disease. Since valproic acid is a long-term treatment. it could be recommended that the incorporation of measurements of lipids, lipoproteins, apolipoproteins and trace elements in the “follow up” laboratory testing could be a preventive measure