RESUMEN
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.
Asunto(s)
Síndromes de Inmunodeficiencia/genética , Proteínas Represoras/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Preescolar , Aberraciones Cromosómicas , Cromosomas Humanos/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN , Análisis Mutacional de ADN , Cara/anomalías , Cara/patología , Femenino , Eliminación de Gen , Pruebas Genéticas/métodos , Humanos , Síndromes de Inmunodeficiencia/patología , Líbano , Masculino , Datos de Secuencia Molecular , Mutación , Linaje , Enfermedades de Inmunodeficiencia Primaria , ADN Metiltransferasa 3BRESUMEN
We report on a young male with mental retardation, slightly upslanting palpebral fissures, strabismus, high-arched palate, retrognathia, and flat feet. Cytogenetic analysis in addition to fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) showed the presence of a chromosome 10p11.2-->p12.2 duplication. Karyotypes of the parents were normal. Comparison of the clinical findings observed in the present patient with those observed in other reported cases with duplication 10p suggest that the presence of high arched/cleft palate and retrognathia may be related to the 10p11.2-->p12.2 duplication. Also, no critical region for the trisomy 10p syndrome has been delimited.