Objective: We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects. Methods: In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/maleZ2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery. Results: OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P!0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (PZ0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (rZ0.295, rZ0.20, P!0.05) and after adjustment for age (rZ 0.28, rZ0.20, P!0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (rZ0.30, P!0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (PZ0.02, PZ0.006, PZ0.007, P!0.001, P!0.001, P!0.001 respectively) and a significant increase in adiponectin and HDL values (P!0.001 for both variables). Conclusion: Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.

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The immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disease characterized by targeted chromosome breakage, directly related to a genomic methylation defect. It manifests with phenotypic and clinical variability, with the most consistent features being developmental delay, facial anomalies, cytogenetic defects and immunodeficiency with a reduction in serum immunoglobulin levels. From the molecular point of view, ICF syndrome was always divided into ICF type I (ICF1) and ICF type 2 (ICF2). Mutations in DNMT3B gene are responsible for ICF1, while mutations in ZBTB24 have been reported to be responsible for ICF2. In this study, we describe a Lebanese family with three ICF2 affected brothers. Sanger sequencing of the coding sequence of ZBTB24 gene was conducted and revealed a novel deletion: c.396_397delTA (p.His132Glnfs*19), resulting in a loss-of-function of the corresponding protein. ZBTB24 belongs to a large family of transcriptional factors and may be involved in DNA methylation of juxtacentromeric DNA. Detailed molecular and functional studies of the ZBTB24 and DNMT3B genes are needed to understand the pathophysiology of ICF syndrome.

Congenital afibrinogenemia, the most severe form of fibrinogen deficiency, is characterized by the complete absence of fibrinogen. The disease is caused by mutations in 1 of the 3 fibrinogen genes FGG, FGA, and FGB, clustered on the long arm of human chromosome 4. The majority of cases are due to null mutations in the FGA gene although one would expect the 3 genes to be equally implicated. However, most patients studied so far are white, and therefore the identification of causative mutations in non-European families is necessary to establish if this finding holds true in all ethnic groups. In this study, we report the identification of a novel nonsense mutation (Arg134Xaa) in the FGG gene responsible for congenital afibrinogenemia in 10 patients from Lebanon. Expression studies in COS-7 cells demonstrated that the Arg134Xaa codon, which is encoded by adjacent exons (TG-intron 4-A) affected neither mRNA splicing nor stability, but led to the production of an unstable, severely truncated fibrinogen ␥ chain that is not incorporated into a functional fibrinogen hexamer. ( IntroductionInherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenemia and afibrinogenemia) or the quality (dysfibrinogenemia) of circulating fibrinogen. Fibrinogen is produced in the liver from 3 homologous polypeptide chains, A␣, B␤, and ␥, which assemble to form a hexamer containing 2 copies of each chain. Fibrinogen is the precursor of fibrin, the major protein constituent of the blood clot. Congenital afibrinogenemia (OMIM: online Mendelian Inheritance in Man; no. 202400), 1 the most severe form of fibrinogen deficiency, is characterized by the complete absence of fibrinogen. The disease was originally described in 1920; 2 it has an estimated prevalence of around 1 to 2 in 1 000 000. Umbilical cord hemorrhage is often the first sign of the disorder; gum bleeding, epistaxis, menorrhagia, gastrointestinal bleeding, and hemarthrosis occur with varying intensity, and spontaneous intracerebral bleeding and splenic rupture can occur throughout life. 3,4 Congenital afibrinogenemia is inherited in an autosomal recessive manner: the condition exists only when both alleles are mutated, in homozygosity or compound heterozygosity; both sexes are affected. Although the disease was first described in 1920, the genetic locus responsible for the disorder was only recently determined. We identified the first causative mutations for this disorder in a nonconsanguineous Swiss family. The genetic defect was an apparently recurrent deletion of approximately 11 kb of DNA that eliminates the majority of the FGA gene and so leads to a complete absence of functional fibrinogen. 5 The deletions were all identical to the base pair and probably resulted from nonhomologous (illegitimate) recombination, mediated by a direct 7 bp repeat, AACTTTT, and perhaps also by indirect repeats in the breakpoint region. Many families with this disorder have been studied since then, allowing the identification of numerous causative mutations (reviewe...