Connor P Craig1,2, Emily Calamaro3, Chin-To Fong3, Anwar M Iqbal1, Alexander R Paciorkowski3,4,5,6, Bin Zhang7,8. 1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. 2. School of Medicine and Dentistry, University of Rochester, 601 Elmwood Ave, Rochester, NY, 14642, USA. 3. Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. 4. Department of Neurology, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. 5. Center for Neural Development and Disease, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. 6. Departments of Neuroscience and Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. 7. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. bin_zhang@urmc.rochester.edu. 8. Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, 14642, USA. bin_zhang@urmc.rochester.edu.
Abstract
BACKGROUND: The FOXG1 gene plays a vital role in mammalian brain differentiation and development. Intra- and intergenic mutations resulting in loss of function or altered expression of the FOXG1 gene cause FOXG1 syndrome. The hallmarks of this syndrome are severe developmental delay with absent verbal language, post-natal growth restriction, post-natal microcephaly, and a recognizable movement disorder characterized by chorea and dystonia. CASE PRESENTATION: Here we describe a case of a 7-year-old male patient found to have a de novo balanced translocation between chromosome 3 at band 3q14.1 and chromosome 14 at band 14q12 via G-banding chromosome and Fluorescence In Situ Hybridization (FISH) analyses. This rearrangement disrupts the proximity of FOXG1 to a previously described smallest region of deletion overlap (SRO), likely resulting in haploinsufficiency. CONCLUSIONS: This case adds to the growing body of literature implicating chromosomal structural variants in the manifestation of this disorder and highlights the vital role of cis-acting regulatory elements in the normal expression of this gene. Finally, we propose a protocol for reflex FISH analysis to improve diagnostic efficiency for patients with suspected FOXG1 syndrome.
BACKGROUND: The FOXG1 gene plays a vital role in mammalian brain differentiation and development. Intra- and intergenic mutations resulting in loss of function or altered expression of the FOXG1 gene cause FOXG1 syndrome. The hallmarks of this syndrome are severe developmental delay with absent verbal language, post-natal growth restriction, post-natal microcephaly, and a recognizable movement disorder characterized by chorea and dystonia. CASE PRESENTATION: Here we describe a case of a 7-year-old male patient found to have a de novo balanced translocation between chromosome 3 at band 3q14.1 and chromosome 14 at band 14q12 via G-banding chromosome and Fluorescence In Situ Hybridization (FISH) analyses. This rearrangement disrupts the proximity of FOXG1 to a previously described smallest region of deletion overlap (SRO), likely resulting in haploinsufficiency. CONCLUSIONS: This case adds to the growing body of literature implicating chromosomal structural variants in the manifestation of this disorder and highlights the vital role of cis-acting regulatory elements in the normal expression of this gene. Finally, we propose a protocol for reflex FISH analysis to improve diagnostic efficiency for patients with suspected FOXG1 syndrome.
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