title: A novel deletion in ZBTB24 in a Lebanese family with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2.
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.
authors: Unité de Génétique Médicale et Laboratoire Associé INSERM à l'unité UMR_S 910, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors: E
authors: E
authors: Chouery
authors: J
authors: J
authors: Abou-Ghoch
authors: S
authors: S
authors: Corbani
authors: N
authors: N
authors: El Ali
authors: R
authors: R
authors: Korban
authors: N
authors: N
authors: Salem
authors: C
authors: C
authors: Castro
authors: S
authors: S
authors: Klayme
authors: M
authors: M
authors: Azoury-Abou Rjeily
authors: R
authors: R
authors: Khoury-Matar
authors: G
authors: G
authors: Debo
authors: M
authors: M
authors: Germanos-Haddad
authors: V
authors: V
authors: Delague
authors: G
authors: G
authors: Lefranc
authors: A
authors: A
authors: Mégarbané
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000473:pathology; D007861:Lebanon; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D000081207:Primary Immunodeficiency Diseases; D012097:Repressor Proteins / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B; C560314:ZBTB24 protein, human