Human Brain Factor 1, a New Member of the Fork Head Gene Family

Murphy, Derek; Wiese, Stefan; Burfeind, Peter; Schmundt, Daphne; Matteï, Marie‐Geneviève; Schulz‐Schaeffer, Walter; Thies, Ulrike

doi:10.1006/geno.1994.1313

Cited by 74 publications

(50 citation statements)

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“…9 FOXG1 is a transcriptional repressor with expression restricted to fetal and adult brain and testis. 32 In addition, overlapping expression of FOXG1 and MECP2 has been demonstrated in differentiating forebrain cortex. 17 FoxG1 is hypothesised to protect Figure 2 Expression of PRKD1 and FOXG1 in 14q12 microdeletion patients.…”

Section: Discussionmentioning

confidence: 99%

14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype

Ellaway

Bettella

et al. 2012

Eur J Hum Genet

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Rett syndrome is a clinically defined neurodevelopmental disorder almost exclusively affecting females. Usually sporadic, Rett syndrome is caused by mutations in the X-linked MECP2 gene in B90-95% of classic cases and 40-60% of individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant. We report the clinical features and array CGH findings of three atypical Rett syndrome patients who had severe intellectual impairment, early-onset developmental delay, postnatal microcephaly and hypotonia. In addition, the females had a seizure disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were found to have an interstitial deletion of 14q12. The deleted region in common included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis suggested a decrease in FOXG1 levels in two of the patients. Screening of 32 atypical Rett syndrome patients did not identify any pathogenic mutations in the PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1 (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett syndrome variant. There is phenotypic overlap between congenital Rett syndrome variants with FOXG1 mutations and the clinical presentation of our three patients with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that the primary defect in these patients is misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1.

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Section: Discussionmentioning

confidence: 99%

14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype

Ellaway

Bettella

et al. 2012

Eur J Hum Genet

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“…It encodes a transcriptional repressor protein with expression restricted to fetal and adult brain, and testis. 18 In the developing brain, FOXG1 expression is restricted to the telencephalic neuroepithelium and the nasal half of the retina and optic stalk. FOXG1 defines the region that will become the telencephalon.…”

Section: Discussionmentioning

confidence: 99%

Atypical Rett syndrome with selective FOXG1 deletion detected by comparative genomic hybridization: case report and review of literature

et al. 2009

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Rett syndrome is a severe neurodegenerative disorder characterized by acquired microcephaly, communication dysfunction, psychomotor regression, seizures and stereotypical hand movements. Mutations in methyl CpG binding protein 2 (MECP2) are identified in most patients with classic Rett syndrome. Genetic studies in patients with a Rett variant have expanded the spectrum of underlying genetic etiologies. Recently, a deletion encompassing several genes in the long arm of chromosome 14 has been associated with the congenital Rett-syndrome phenotype. Using array-based comparative genomic hybridization, we identified a 3-year-old female with a Rett-like syndrome carrying a de novo single-gene deletion of FOXG1. Her presentation included intellectual disability, epilepsy and a Rett-like phenotype. The variant features included microcephaly at birth and prominent synophrys. Our results confirm that congenital Rett syndrome can be caused by copy-number variation in FOXG1 and expand the clinical phenotypic spectrum of FOXG1 defect in humans.

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“…Three factors have a major influence on the cellular output from the proliferative zones: the rate of cell proliferation, the rate of cell differentiation, and the rate of cell death. The progenitor cells of the telencephalon are identifiable as early as the eight-somite stage (E8.5) by the expression of one of the members of the forkhead box family, the FoxG1 transcription factor, also known as the winged-helix (WH) protein brain factor (BF-1) [Murphy et al, 1994].…”

Section: Introductionmentioning

confidence: 99%

A missense mutation within the fork-head domain of the forkhead box G1 Gene (FOXG1) affects its nuclear localization

et al. 2010

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ABSTRACT:The forkhead box G1 (FOXG1) gene has recently been associated with the congenital variant of Rett syndrome, and so far 17 mutations have been reported. We screened the coding region in 150 patients affected by postnatal microcephaly, and identified two mutations: the c.326C>T (p.P109L) substitution inherited from the healthy father; and the de novo c.730C>T transition, which induces the p.R244C mutation within the DNA-binding forkhead domain. This latter mutation is carried by an 8-year-old girl, who presented a phenotype reminiscent of the congenital variant of Rett syndrome. Immunofluorescence analysis of the wild-type protein revealed a homogeneous nuclear staining excluding the nucleoli, while the p.R244C mutant showed abnormal nuclear foci in a large proportion of cells, suggesting that its mislocalization may reduce and/or impair target recognition. Interestingly, this missense mutation results in a mislocalization of FoxG1 to specific nuclear foci referred to as nuclear speckles, and affects the cyclin-dependent kinase inhibitor p21 CDKN1A expression. Because CDKL5, which is involved in the early-onset variant of Rett syndrome, is also located in these speckles, we suggest that disregulation of the dynamic behaviour of nuclear speckles may functionally link these two proteins, which are both involved in atypical forms of Rett syndrome.

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Human Brain Factor 1, a New Member of the Fork Head Gene Family

Cited by 74 publications

References 0 publications

14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype

14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype

Atypical Rett syndrome with selective FOXG1 deletion detected by comparative genomic hybridization: case report and review of literature

A missense mutation within the fork-head domain of the forkhead box G1 Gene (FOXG1) affects its nuclear localization

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