Velo-cardio-facial syndrome (VCFS) is a autosomal dominant disorder. Patients with this disorder have a spectrum of abnormalities which include: cleft palate, speech and learning disabilities, typical facial appearances and cardiac defects. Our cytogenetic and molecular analysis of a group of VCFS patients provides insights into its genetic basis. Submicroscopic deletion of 22q11 have been found in approximately 90% of patients studied. Our findings support the use of molecular or molecular-cytogenetic analysis for the diagnosis of patients with VCFS. However, understanding the pathogenesis of this disorder will require identification of the deleted genes and investigations into the role that these genes play in normal embryonic and postnatal development. Finally, the role of the specific genes in the developing embryo can be manipulated in a mouse model to determine the developmental etiology of VCFS. Hence, a consortium of experienced basic scientists and clinical investigators at the Children's Hosp. of Phila, Wistar Institute, the Children's Seashore House, the Univs. of Penna. and Oklahoma have established a program dedicated to a multidisciplinary clinical and laboratory-based investigation of VCFS. The latest technologies in molecular genetics, clinical genetics, developmental biology and physical diagnosis will be applied to this syndrome. Thus, Project 1 will pursue several molecular approaches directed at gene identification (cDNA capture and exon prediction from DNA sequence). Project 2 will examine these genes in the developing mouse embryo to determine temporal and spatial expression during development (mouse embryo culture system). Using the molecular-diagnostic and screening tests (PCR and fluorescence in situ hybridization) which will be developed and applied by Project 3, a coordinated approach, combining comprehensive physical examination and laboratory-based testing will improve the specificity of diagnosis. This will result in the development of objective phenotypic criteria which will aid clinicians in recognizing at risk patients. Early diagnosis of VCFS will allow timely intervention to optimize speech and language development and to avoid some of the stigmata encountered as a result of defective communication skills. This program represents a team effort aimed at: molecular characterization of the deleted region 22q11 in VCFS, identification of the significant genes responsible for the VCFS phenotype and examination of the role that these genes play in normal and abnormal development.
| Belangero, Sintia Iole Nogueira; Bellucco, Fernanda Teixeira da Silva; Cernach, Mirlene C S P et al. (2009) Interrupted aortic arch type B in A patient with cat eye syndrome. Arq Bras Cardiol 92:e29-31, e56-8 |
| Goldmuntz, Elizabeth; Driscoll, Deborah A; Emanuel, Beverly S et al. (2009) Evaluation of potential modifiers of the cardiac phenotype in the 22q11.2 deletion syndrome. Birth Defects Res A Clin Mol Teratol 85:125-9 |
| Bearden, Carrie E; van Erp, Theo G M; Dutton, Rebecca A et al. (2009) Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions. Cereb Cortex 19:115-26 |
| Nogueira, Sintia Iole; Hacker, April M; Bellucco, Fernanda T S et al. (2008) Atypical 22q11.2 deletion in a patient with DGS/VCFS spectrum. Eur J Med Genet 51:226-30 |
| Nogueira, Sintia Iole; Hacker, April M; Bellucco, Fernanda T S et al. (2007) Deletion 22q11.2: report of a complex meiotic mechanism of origin. Am J Med Genet A 143A:1778-81 |
| Vorstman, J A S; Jalali, G R; Rappaport, E F et al. (2006) MLPA: a rapid, reliable, and sensitive method for detection and analysis of abnormalities of 22q. Hum Mutat 27:814-21 |
| Kato, Takema; Inagaki, Hidehito; Yamada, Kouji et al. (2006) Genetic variation affects de novo translocation frequency. Science 311:971 |
| Driscoll, Deborah A; Boland, Torrey; Emanuel, Beverly S et al. (2006) Evaluation of potential modifiers of the palatal phenotype in the 22q11.2 deletion syndrome. Cleft Palate Craniofac J 43:435-41 |
| Ruotolo, Rachel A; Veitia, Nestor A; Corbin, Aaron et al. (2006) Velopharyngeal anatomy in 22q11.2 deletion syndrome: a three-dimensional cephalometric analysis. Cleft Palate Craniofac J 43:446-56 |
| McDonald-McGinn, Donna M; Minugh-Purvis, Nancy; Kirschner, Richard E et al. (2005) The 22q11.2 deletion in African-American patients: an underdiagnosed population? Am J Med Genet A 134:242-6 |
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