ABSTRACT
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.
Subject(s)
Immunologic Deficiency Syndromes/genetics , Repressor Proteins/genetics , Adolescent , Adult , Amino Acid Sequence , Child , Child, Preschool , Chromosome Aberrations , Chromosomes, Human/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methylation , DNA Mutational Analysis , Face/abnormalities , Face/pathology , Female , Gene Deletion , Genetic Testing/methods , Humans , Immunologic Deficiency Syndromes/pathology , Lebanon , Male , Molecular Sequence Data , Mutation , Pedigree , Primary Immunodeficiency Diseases , DNA Methyltransferase 3BABSTRACT
OBJECTIVES: We performed an epidemiological survey to ascertain the clinical features of brucellosis in Lebanon. PATIENTS AND METHODS: Between 1994 and 1998, 63 patients were seen at the Hôtel-Dieu de France Hospital in Beirut Lebanon. Diagnostic criteria were brucellar agglutinins at a titer > or = 1/160 with symptoms suggestive of brucellosis in the absence of another diagnosis. We also conducted a survey in 1138 cases registered by the Ministry of Health during the same period. RESULTS: Among the 1137 cases, 40% of the patients were over 60 and only 16% were under 14. The overall male to female ratio was 1.01 and 69% of the patients were seen in spring and summer. Among the 63 patients, 10 were pediatric cases. The disease was acute in 41 (65%), subacute in 21 (33%) and chronic in 1. The main presenting symptoms were fever, sweating, easy fatigability and joint pain. Osteoarticular involvement was the most prevalent complication (25%), predominantly spondylitis. Among the blood tests, relative lymphocytosis was significantly more frequent in children than adults (80% versus 13%, p < 0.001). CONCLUSION: Brucellosis is still an endemic disease in Lebanon and should be considered notably in patients presenting with prolonged fever, and articular and neurological manifestations.
