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  The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis

Kortum, F., Das, S., Flindt, M., Morris-Rosendahl, D. J., Stefanova, I., Goldstein, A., et al. (2011). The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. J Med Genet, 48(6), 396-406. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21441262 http://jmg.bmj.com/content/48/6/396.full.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-784E-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-784F-2
Genre: Journal Article

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Kortum, F., Author
Das, S., Author
Flindt, M., Author
Morris-Rosendahl, D. J., Author
Stefanova, I., Author
Goldstein, A., Author
Horn, D., Author
Klopocki, E.1, Author              
Kluger, G., Author
Martin, P., Author
Rauch, A., Author
Roumer, A., Author
Saitta, S., Author
Walsh, L. E., Author
Wieczorek, D., Author
Uyanik, G., Author
Kutsche, K., Author
Dobyns, W. B., Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Base Sequence; Child; Child, Preschool; Chromosomes, Human, Pair 14/*chemistry; Comparative Genomic Hybridization; Corpus Callosum/pathology; Dyskinesias/genetics; Female; Forkhead Transcription Factors/*genetics; *Genetic Association Studies; Genotype; Humans; Intellectual Disability/genetics; Male; Methyl-CpG-Binding Protein 2/genetics; Microcephaly/genetics; Molecular Sequence Data; Molecular Typing; Mutation; Nerve Tissue Proteins/*genetics; Phenotype; Rett Syndrome/*classification/*genetics; Sequence Deletion
 Abstract: BACKGROUND: Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients. METHOD: The study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals. RESULTS: One known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria. CONCLUSIONS: These findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome.

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 Dates: 2011
 Publication Status: Published in print
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Title: J Med Genet
Source Genre: Journal
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Pages: - Volume / Issue: 48 (6) Sequence Number: - Start / End Page: 396 - 406 Identifier: ISSN: 1468-6244 (Electronic) 0022-2593 (Linking)