FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms
Abstract
:1. Introduction
FOXG1-Related Syndrome: A Distinct Entity from Rett Syndrome (RTT)
2. Clinical Features of FOXG1-Related Syndrome
2.1. FOXG1-Related Syndrome: Deletions/Intragenic Mutations
2.1.1. Movement Disorders
2.1.2. Epilepsy
2.1.3. Brain Images
2.1.4. Other Comorbidities
2.1.5. Genetic Mutations and Genotype–Phenotype Correlation
2.2. FOXG1-Related Syndrome: Duplication
2.2.1. Movement Disorders
2.2.2. Epilepsy
2.2.3. Brain Images
2.2.4. Genetic Mutations
3. In Vitro Study of Possible Molecular Functions of FOXG1 in Neurons and Other Tissues
4. FOXG1-Related In Vivo Models and Possible Pathogenic Mechanisms
4.1. The Functions of FOXG1 in Neurodevelopment
4.2. The Possible Pathogenic Mechanisms of FOXG1-Related Syndrome
4.2.1. Reduced Volume of Hemisphere with Disrupted Brain Morphology
4.2.2. Imbalance of Inhibitory/Excitatory Neurons and Their Markers
4.2.3. Alteration in Dendritogenesis and Neural Plasticity
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACTH | adrenocorticotrophic hormone |
AIB1 | amplified in breast cancer 1 |
BMI1 | B-cell specific moloneymurine leukemiavirus insertion site 1 |
bp | base pair |
CDKL5 | cyclin-dependent kinase-like 5 |
Cdkn1a | cyclin dependent kinase Inhibitor 1A |
cs | Conserved site |
DG | dentate gyrus |
EEG | electroencephalogram |
EGF | epidermal growth factor |
FBD | forkhead binding domain |
FOXG1 | forkhead box G1 |
FOXO | Forkhead box protein O |
GluD1 | glutamate receptor δ-1 subunit |
GTBD | Groucho-binding domain |
IGF-1 | Insulin-like growth factor 1 |
iPSC | induced pluripotent stem cells |
JBD | JARID1B-binding domain |
Mb | Megabyte |
MECP2 | methyl-CpG-binding protein 2 |
MRI | magnetic resonance imaging |
N/A | Not available |
NSCs | neural stem cells |
p21cip1 | p21 cyclin-dependent kinase inhibitor |
RTT | Rett syndrome |
TGF-β | transforming growth factor-beta |
TLE | transducin-like enhancer of split |
Wnt | Wingless/Integrated |
References
- Jeffrey, L.N.; Kaufmann, W.E.; Glaze, D.G.; Christodoulou, J.; Clarke, A.J.; Bahi-Buisson, N.; Leonard, H.; Bailey, M.E.S.; Schanen, N.C.; Zappella, M.; et al. Rett syndrome: Revised diagnostic criteria and nomenclature. Ann. Neurol. 2010, 68, 944–950. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumamoto, T.; Hanashima, C. Evolutionary conservation and conversion of Foxg1 function in brain development. Dev. Growth Differ. 2017, 59, 258–269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ariani, F.; Hayek, G.; Rondinella, D.; Artuso, R.; Mencarelli, M.A.; Spanhol-Rosseto, A.; Pollazzon, M.; Buoni, S.; Spiga, O.; Ricciardi, S. FOXG1 is responsible for the congenital variant of Rett syndrome. Am. J. Hum. Genet. 2008, 83, 89–93. [Google Scholar] [CrossRef] [PubMed]
- Pontrelli, G.; Cappelletti, S.; Claps, D.; Sirleto, P.; Ciocca, L.; Petrocchi, S.; Terracciano, A.; Serino, D.; Fusco, L.; Vigevano, F.; et al. Epilepsy in patients with duplications of chromosome 14 harboring Foxg1. Pediatr. Neurol. 2014, 50, 530–535. [Google Scholar] [CrossRef] [PubMed]
- Bertossi, C.; Cassina, M.; Cappellari, A.; Toldo, I.; Nosadini, M.; Rigon, C.; Suppiej, A.; Sartori, S. Forkhead box G1 gene haploinsufficiency: An emerging cause of dyskinetic encephalopathy of infancy. Neuropediatrics 2015, 46, 56–64. [Google Scholar] [CrossRef]
- Mitter, D.; Pringsheim, M.; Kaulisch, M.; Plumacher, K.S.; Schroder, S.; Warthemann, R.; Abou Jamra, R.; Baethmann, M.; Bast, T.; Buttel, H.M.; et al. FOXG1 syndrome: Genotype-phenotype association in 83 patients with FOXG1 variants. Genet. Med. 2017. [Google Scholar] [CrossRef]
- Pratt, D.; Warner, J.; Williams, M. Genotyping FOXG1 mutations in patients with clinical evidence of the FOXG1 syndrome. Mol. Syndromol. 2012, 3, 284–287. [Google Scholar] [CrossRef]
- Shoichet, S.A.; Kunde, S.A.; Viertel, P.; Schell-Apacik, C.; von Voss, H.; Tommerup, N.; Ropers, H.H.; Kalscheuer, V.M. Haploinsufficiency of novel FOXG1B variants in a patient with severe mental retardation, brain malformations and microcephaly. Hum. Genet. 2005, 117, 536–544. [Google Scholar] [CrossRef]
- Papandreou, A.; Schneider, R.B.; Augustine, E.F.; Ng, J.; Mankad, K.; Meyer, E.; McTague, A.; Ngoh, A.; Hemingway, C.; Robinson, R.; et al. Delineation of the movement disorders associated with FOXG1 mutations. Neurology 2016, 86, 1794–1800. [Google Scholar] [CrossRef]
- Vegas, N.; Cavallin, M.; Maillard, C.; Boddaert, N.; Toulouse, J.; Schaefer, E.; Lerman-Sagie, T.; Lev, D.; Magalie, B.; Moutton, S.; et al. Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy. Neurol. Genet. 2018, 4, e281. [Google Scholar] [CrossRef]
- Caporali, C.; Signorini, S.; De Giorgis, V.; Pichiecchio, A.; Zuffardi, O.; Orcesi, S. Early-onset movement disorder as diagnostic marker in genetic syndromes: Three cases of FOXG1-related syndrome. Eur. J. Paediatr. Neurol. 2018, 22, 336–339. [Google Scholar] [CrossRef] [PubMed]
- Seltzer, L.E.; Ma, M.; Ahmed, S.; Bertrand, M.; Dobyns, W.B.; Wheless, J.; Paciorkowski, A.R. Epilepsy and outcome in FOXG1-related disorders. Epilepsia 2014, 55, 1292–1300. [Google Scholar] [CrossRef] [PubMed]
- Wong, L.-C.; Wu, Y.-T.; Hsu, C.-J.; Weng, W.-C.; Tsai, W.-C.; Lee, W.-T. Cognition and Evolution of Movement Disorders of FOXG1-Related Syndrome. Front. Neurol. 2019, 10. [Google Scholar] [CrossRef] [PubMed]
- De Bruyn, C.; Vanderhasselt, T.; Tanyalcin, I.; Keymolen, K.; Van Rompaey, K.L.; De Meirleir, L.; Jansen, A.C. Thin genu of the corpus callosum points to mutation in FOXG1 in a child with acquired microcephaly, trigonocephaly, and intellectual developmental disorder: A case report and review of literature. Eur. J. Paediatr. Neurol. 2014, 18, 420–426. [Google Scholar] [CrossRef] [PubMed]
- Kortüm, F.; Das, S.; Flindt, M.; Morris-Rosendahl, D.J.; Stefanova, I.; Goldstein, A.; Horn, D.; Klopocki, E.; Kluger, G.; Martin, P. The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. J. Med. Genet. 2011, 48, 396–406. [Google Scholar] [CrossRef]
- Zhang, Q.; Wang, J.; Li, J.; Bao, X.; Zhao, Y.; Zhang, X.; Wei, L.; Wu, X. Novel FOXG1 mutations in Chinese patients with Rett syndrome or Rett-like mental retardation. BMC Med. Genet. 2017, 18, 96. [Google Scholar] [CrossRef] [PubMed]
- Yeung, A.; Bruno, D.; Scheffer, I.E.; Carranza, D.; Burgess, T.; Slater, H.R.; Amor, D.J. 4.45 Mb microduplication in chromosome band 14q12 including FOXG1 in a girl with refractory epilepsy and intellectual impairment. Eur. J. Med. Genet. 2009, 52, 440–442. [Google Scholar] [CrossRef] [PubMed]
- Brunetti-Pierri, N.; Paciorkowski, A.R.; Ciccone, R.; Della Mina, E.; Bonaglia, M.C.; Borgatti, R.; Schaaf, C.P.; Sutton, V.R.; Xia, Z.; Jelluma, N.; et al. Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. Eur. J. Hum. Genet. 2011, 19, 102–107. [Google Scholar] [CrossRef]
- Paciorkowski, A.R.; Thio, L.L.; Rosenfeld, J.A.; Gajecka, M.; Gurnett, C.A.; Kulkarni, S.; Chung, W.K.; Marsh, E.D.; Gentile, M.; Reggin, J.D.; et al. Copy number variants and infantile spasms: Evidence for abnormalities in ventral forebrain development and pathways of synaptic function. Eur. J. Hum. Genet. 2011, 19, 1238–1245. [Google Scholar] [CrossRef] [PubMed]
- Striano, P.; Paravidino, R.; Sicca, F.; Chiurazzi, P.; Gimelli, S.; Coppola, A.; Robbiano, A.; Traverso, M.; Pintaudi, M.; Giovannini, S.; et al. West syndrome associated with 14q12 duplications harboring FOXG1. Neurology 2011, 76, 1600–1602. [Google Scholar] [CrossRef]
- Tohyama, J.; Yamamoto, T.; Hosoki, K.; Nagasaki, K.; Akasaka, N.; Ohashi, T.; Kobayashi, Y.; Saitoh, S. West syndrome associated with mosaic duplication of FOXG1 in a patient with maternal uniparental disomy of chromosome 14. Am. J. Med. Genet. A 2011, 155a, 2584–2588. [Google Scholar] [CrossRef] [PubMed]
- Amor, D.J.; Burgess, T.; Tan, T.Y.; Pertile, M.D. Questionable pathogenicity of FOXG1 duplication. Eur. J. Hum. Genet. 2012, 20, 595–596. [Google Scholar] [CrossRef] [PubMed]
- Bertossi, C.; Cassina, M.; De Palma, L.; Vecchi, M.; Rossato, S.; Toldo, I.; Dona, M.; Murgia, A.; Boniver, C.; Sartori, S. 14q12 duplication including FOXG1: Is there a common age-dependent epileptic phenotype? Brain Dev. 2014, 36, 402–407. [Google Scholar] [CrossRef] [PubMed]
- Helbig, K.L.; Farwell Hagman, K.D.; Shinde, D.N.; Mroske, C.; Powis, Z.; Li, S.; Tang, S.; Helbig, I. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet. Med. 2016, 18, 898–905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cetin, O.E.; Yalcinkaya, C.; Karaman, B.; Demirbilek, V.; Tuysuz, B. Chromosome 14q11.2-q21.1 duplication: A rare cause of West syndrome. Epileptic Disord. 2018, 20, 219–224. [Google Scholar] [CrossRef] [PubMed]
- Vineeth, V.S.; Dutta, U.R.; Tallapaka, K.; Das Bhowmik, A.; Dalal, A. Whole exome sequencing identifies a novel 5Mb deletion at 14q12 region in a patient with global developmental delay, microcephaly and seizures. Gene 2018, 673, 56–60. [Google Scholar] [CrossRef] [PubMed]
- Boggio, E.M.; Pancrazi, L.; Gennaro, M.; Lo Rizzo, C.; Mari, F.; Meloni, I.; Ariani, F.; Panighini, A.; Novelli, E.; Biagioni, M.; et al. Visual impairment in FOXG1-mutated individuals and mice. Neuroscience 2016, 324, 496–508. [Google Scholar] [CrossRef]
- Manuel, M.; Martynoga, B.; Yu, T.; West, J.D.; Mason, J.O.; Price, D.J. The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice. Development 2010, 137, 487–497. [Google Scholar] [CrossRef] [Green Version]
- Cargnin, F.; Kwon, J.S.; Katzman, S.; Chen, B.; Lee, J.W.; Lee, S.K. FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections. Neuron 2018, 100, 1083–1096. [Google Scholar] [CrossRef]
- Vezzali, R.; Weise, S.C.; Hellbach, N.; Machado, V.; Heidrich, S.; Vogel, T. The FOXG1/FOXO/SMAD network balances proliferation and differentiation of cortical progenitors and activates Kcnh3 expression in mature neurons. Oncotarget 2016, 7, 37436–37455. [Google Scholar] [CrossRef] [Green Version]
- Hanashima, C.; Fernandes, M.; Hebert, J.M.; Fishell, G. The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J. Neurosci. 2007, 27, 11103–11111. [Google Scholar] [CrossRef] [PubMed]
- Mariani, J.; Coppola, G.; Zhang, P.; Abyzov, A.; Provini, L.; Tomasini, L.; Amenduni, M.; Szekely, A.; Palejev, D.; Wilson, M.; et al. FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders. Cell 2015, 162, 375–390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Patriarchi, T.; Amabile, S.; Frullanti, E.; Landucci, E.; Lo Rizzo, C.; Ariani, F.; Costa, M.; Olimpico, F.; Hell, J.W.; Vaccarino, F.M.; et al. Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1(+/−) patients and in foxg1(+/−) mice. Eur. J. Hum. Genet. 2016, 24, 871–880. [Google Scholar] [CrossRef] [PubMed]
- Chiola, S.; Do, M.D.; Centrone, L.; Mallamaci, A. Foxg1 Overexpression in Neocortical Pyramids Stimulates Dendrite Elongation Via Hes1 and pCreb1 Upregulation. Cereb. Cortex 2019, 29, 1006–1019. [Google Scholar] [CrossRef] [PubMed]
- Dastidar, S.G.; Landrieu, P.M.; D’Mello, S.R. FoxG1 promotes the survival of postmitotic neurons. J. Neurosci. 2011, 31, 402–413. [Google Scholar] [CrossRef] [PubMed]
- Yu, B.; Liu, J.; Su, M.; Wang, C.; Chen, H.; Zhao, C. Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects. Mol. Brain 2019, 12, 63. [Google Scholar] [CrossRef] [PubMed]
- Tian, C.; Gong, Y.; Yang, Y.; Shen, W.; Wang, K.; Liu, J.; Xu, B.; Zhao, J.; Zhao, C. Foxg1 has an essential role in postnatal development of the dentate gyrus. J. Neurosci. 2012, 32, 2931–2949. [Google Scholar] [CrossRef]
- Cellini, E.; Vignoli, A.; Pisano, T.; Falchi, M.; Molinaro, A.; Accorsi, P.; Bontacchio, A.; Pinelli, L.; Giordano, L.; Guerrini, R. The hyperkinetic movement disorder of FOXG1-related epileptic-dyskinetic encephalopathy. Dev. Med. Child. Neurol. 2016, 58, 93–97. [Google Scholar] [CrossRef]
- Chin Wong, L.; Hung, P.L.; Jan, T.Y.; Lee, W.T. Variations of stereotypies in individuals with Rett syndrome: A nationwide cross-sectional study in Taiwan. Autism Res. Off. J. Int. Soc. Autism Res. 2017, 10, 1204–1214. [Google Scholar] [CrossRef]
- Carecchio, M.; Mencacci, N.E. Emerging Monogenic Complex Hyperkinetic Disorders. Curr. Neurol. Neurosci. Rep. 2017, 17, 97. [Google Scholar] [CrossRef]
- Guerrini, R.; Parrini, E. Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies. Epilepsia 2012, 53, 2067–2078. [Google Scholar] [CrossRef]
- Terrone, G.; Bienvenu, T.; Germanaud, D.; Barthez-Carpentier, M.A.; Diebold, B.; Delanoe, C.; Passemard, S.; Auvin, S. A case of Lennox-Gastaut syndrome in a patient with FOXG1-related disorder. Epilepsia 2014, 55, e116–e119. [Google Scholar] [CrossRef]
- Allou, L.; Lambert, L.; Amsallem, D.; Bieth, E.; Edery, P.; Destree, A.; Rivier, F.; Amor, D.; Thompson, E.; Nicholl, J.; et al. 14q12 and severe Rett-like phenotypes: New clinical insights and physical mapping of FOXG1-regulatory elements. Eur. J. Hum. Genet. 2012, 20, 1216–1223. [Google Scholar] [CrossRef]
- Van der Aa, N.; Van den Bergh, M.; Ponomarenko, N.; Verstraete, L.; Ceulemans, B.; Storm, K. Analysis of FOXG1 Is Highly Recommended in Male and Female Patients with Rett Syndrome. Mol. Syndr. 2011, 1, 290–293. [Google Scholar] [CrossRef]
- De Filippis, R.; Pancrazi, L.; Bjørgo, K.; Rosseto, A.; Kleefstra, T.; Grillo, E.; Panighini, A.; Cardarelli, F.; Meloni, I.; Ariani, F.; et al. Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin-binding dynamics. Clin. Genet. 2011, 82, 395–403. [Google Scholar] [CrossRef]
- McMahon, K.Q.; Papandreou, A.; Ma, M.; Barry, B.J.; Mirzaa, G.M.; Dobyns, W.B.; Scott, R.H.; Trump, N.; Kurian, M.A.; Paciorkowski, A.R. Familial recurrences of FOXG1-related disorder: Evidence for mosaicism. Am. J. Med. Genet. A 2015, 167a, 3096–3102. [Google Scholar] [CrossRef]
- Le Guen, T.; Bahi-Buisson, N.; Nectoux, J.; Boddaert, N.; Fichou, Y.; Diebold, B.; Desguerre, I.; Raqbi, F.; Daire, V.C.; Chelly, J.; et al. A FOXG1 mutation in a boy with congenital variant of Rett syndrome. Neurogenetics 2011, 12, 1–8. [Google Scholar] [CrossRef]
- Takahashi, S.; Matsumoto, N.; Okayama, A.; Suzuki, N.; Araki, A.; Okajima, K.; Tanaka, H.; Miyamoto, A. FOXG1 mutations in Japanese patients with the congenital variant of Rett syndrome. Clin. Genet. 2012, 82, 569–573. [Google Scholar] [CrossRef]
- Meneret, A.; Mignot, C.; An, I.; Habert, M.O.; Jacquette, A.; Vidailhet, M.; Bienvenu, T.; Roze, E. Generalized dystonia, athetosis, and parkinsonism associated with FOXG1 mutation. Mov. Disord. 2012, 27, 160–161. [Google Scholar] [CrossRef]
- Zhang, Q.; Yang, X.; Wang, J.; Li, J.; Wu, Q.; Wen, Y.; Zhao, Y.; Zhang, X.; Yao, H.; Wu, X.; et al. Genomic mosaicism in the pathogenesis and inheritance of a Rett syndrome cohort. Genet. Med. 2019, 21, 1330–1338. [Google Scholar] [CrossRef]
- Harada, K.; Yamamoto, M.; Konishi, Y.; Koyano, K.; Takahashi, S.; Namba, M.; Kusaka, T. Hypoplastic hippocampus in atypical Rett syndrome with a novel FOXG1 mutation. Brain Dev. 2018, 40, 49–52. [Google Scholar] [CrossRef]
- Le Guen, T.; Fichou, Y.; Nectoux, J.; Bahi-Buisson, N.; Rivier, F.; Boddaert, N.; Diebold, B.; Heron, D.; Chelly, J.; Bienvenu, T. A missense mutation within the fork-head domain of the forkhead box G1 Gene (FOXG1) affects its nuclear localization. Hum. Mutat. 2011, 32, E2026–E2035. [Google Scholar] [CrossRef]
- Olson, H.E.; Tambunan, D.; LaCoursiere, C.; Goldenberg, M.; Pinsky, R.; Martin, E.; Ho, E.; Khwaja, O.; Kaufmann, W.E.; Poduri, A. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. Am. J. Med. Genet. A 2015, 167a, 2017–2025. [Google Scholar] [CrossRef]
- Mencarelli, M.A.; Spanhol-Rosseto, A.; Artuso, R.; Rondinella, D.; De Filippis, R.; Bahi-Buisson, N.; Nectoux, J.; Rubinsztajn, R.; Bienvenu, T.; Moncla, A.; et al. Novel FOXG1 mutations associated with the congenital variant of Rett syndrome. J. Med. Genet. 2010, 47, 49–53. [Google Scholar] [CrossRef]
- Das, D.K.; Jadhav, V.; Ghattargi, V.C.; Udani, V. Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome. Gene 2014, 538, 109–112. [Google Scholar] [CrossRef]
- Ma, M.; Adams, H.R.; Seltzer, L.E.; Dobyns, W.B.; Paciorkowski, A.R. Phenotype Differentiation of FOXG1 and MECP2 Disorders: A New Method for Characterization of Developmental Encephalopathies. J. Pediatr. 2016, 178, 233–240. [Google Scholar] [CrossRef]
- Philippe, C.; Amsallem, D.; Francannet, C.; Lambert, L.; Saunier, A.; Verneau, F.; Jonveaux, P. Phenotypic variability in Rett syndrome associated with FOXG1 mutations in females. J. Med. Genet. 2010, 47, 59–65. [Google Scholar] [CrossRef]
- Bahi-Buisson, N.; Nectoux, J.; Girard, B.; Van Esch, H.; De Ravel, T.; Boddaert, N.; Plouin, P.; Rio, M.; Fichou, Y.; Chelly, J.; et al. Revisiting the phenotype associated with FOXG1 mutations: Two novel cases of congenital Rett variant. Neurogenetics 2010, 11, 241–249. [Google Scholar] [CrossRef]
- Diebold, B.; Delepine, C.; Nectoux, J.; Bahi-Buisson, N.; Parent, P.; Bienvenu, T. Somatic mosaicism for a FOXG1 mutation: Diagnostic implication. Clin. Genet. 2014, 85, 589–591. [Google Scholar] [CrossRef]
- Vidal, S.; Brandi, N.; Pacheco, P.; Gerotina, E.; Blasco, L.; Trotta, J.R.; Derdak, S.; Del Mar O’Callaghan, M.; Garcia-Cazorla, A.; Pineda, M.; et al. The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome. Sci. Rep. 2017, 7, 12288. [Google Scholar] [CrossRef]
- Ellaway, C.J.; Ho, G.; Bettella, E.; Knapman, A.; Collins, F.; Hackett, A.; McKenzie, F.; Darmanian, A.; Peters, G.B.; Fagan, K.; et al. 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype. Eur. J. Hum. Genet. 2013, 21, 522–527. [Google Scholar] [CrossRef]
- Takagi, M.; Sasaki, G.; Mitsui, T.; Honda, M.; Tanaka, Y.; Hasegawa, T. A 2.0 Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum. Eur. J. Med. Genet. 2013, 56, 526–528. [Google Scholar] [CrossRef]
- Yoon, J.G.; Shin, S.; Jung, J.W.; Lee, S.-T.; Choi, J.R. An 18.3-Mb Duplication on Chromosome 14q With Multiple Cardiac Anomalies and Clubfoot Was Identified by Microarray Analysis. Ann. Lab. Med. 2016, 36, 194–196. [Google Scholar] [CrossRef]
- Jimenez-Legido, M.; Garcia-Penas, J.J. [West syndrome associated with 14q12 duplication]. Rev. Neurol. 2017, 65, 430–432. [Google Scholar]
- Fasano, C.A.; Phoenix, T.N.; Kokovay, E.; Lowry, N.; Elkabetz, Y.; Dimos, J.T.; Lemischka, I.R.; Studer, L.; Temple, S. Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev. 2009, 23, 561–574. [Google Scholar] [CrossRef] [Green Version]
- Manoranjan, B.; Wang, X.; Hallett, R.M.; Venugopal, C.; Mack, S.C.; McFarlane, N.; Nolte, S.M.; Scheinemann, K.; Gunnarsson, T.; Hassell, J.A.; et al. FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells. Stem Cells 2013, 31, 1266–1277. [Google Scholar] [CrossRef]
- Dou, C.; Lee, J.; Liu, B.; Liu, F.; Massague, J.; Xuan, S.; Lai, E. BF-1 interferes with transforming growth factor beta signaling by associating with Smad partners. Mol. Cell. Biol. 2000, 20, 6201–6211. [Google Scholar] [CrossRef]
- Rodriguez, C.; Huang, L.J.; Son, J.K.; McKee, A.; Xiao, Z.; Lodish, H.F. Functional cloning of the proto-oncogene brain factor-1 (BF-1) as a Smad-binding antagonist of transforming growth factor-beta signaling. J. Biol. Chem. 2001, 276, 30224–30230. [Google Scholar] [CrossRef]
- Brancaccio, M.; Pivetta, C.; Granzotto, M.; Filippis, C.; Mallamaci, A. Emx2 and Foxg1 inhibit gliogenesis and promote neuronogenesis. Stem Cells 2010, 28, 1206–1218. [Google Scholar] [CrossRef]
- Danesin, C.; Peres, J.N.; Johansson, M.; Snowden, V.; Cording, A.; Papalopulu, N.; Houart, C. Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1. Dev. Cell 2009, 16, 576–587. [Google Scholar] [CrossRef]
- Adesina, A.M.; Veo, B.L.; Courteau, G.; Mehta, V.; Wu, X.; Pang, K.; Liu, Z.; Li, X.N.; Peters, L. FOXG1 expression shows correlation with neuronal differentiation in cerebellar development, aggressive phenotype in medulloblastomas, and survival in a xenograft model of medulloblastoma. Hum. Pathol. 2015, 46, 1859–1871. [Google Scholar] [CrossRef]
- Verginelli, F.; Perin, A.; Dali, R.; Fung, K.H.; Lo, R.; Longatti, P.; Guiot, M.C.; Del Maestro, R.F.; Rossi, S.; di Porzio, U.; et al. Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth. Nat. Commun. 2013, 4, 2956. [Google Scholar] [CrossRef]
- He, Z.; Fang, Q.; Li, H.; Shao, B.; Zhang, Y.; Zhang, Y.; Han, X.; Guo, R.; Cheng, C.; Guo, L.; et al. The role of FOXG1 in the postnatal development and survival of mouse cochlear hair cells. Neuropharmacology 2019, 144, 43–57. [Google Scholar] [CrossRef]
- Adesina, A.M.; Nguyen, Y.; Guanaratne, P.; Pulliam, J.; Lopez-Terrada, D.; Margolin, J.; Finegold, M. FOXG1 is overexpressed in hepatoblastoma. Hum. Pathol. 2007, 38, 400–409. [Google Scholar] [CrossRef]
- Adesina, A.M.; Nguyen, Y.; Mehta, V.; Takei, H.; Stangeby, P.; Crabtree, S.; Chintagumpala, M.; Gumerlock, M.K. FOXG1 dysregulation is a frequent event in medulloblastoma. J. Neurooncol. 2007, 85, 111–122. [Google Scholar] [CrossRef]
- Chen, J.; Wu, X.; Xing, Z.; Ma, C.; Xiong, W.; Zhu, X.; He, X. FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis. J. Cancer 2018, 9, 778–783. [Google Scholar] [CrossRef]
- Li, J.V.; Chien, C.D.; Garee, J.P.; Xu, J.; Wellstein, A.; Riegel, A.T. Transcriptional repression of AIB1 by FoxG1 leads to apoptosis in breast cancer cells. Mol. Endocrinol. 2013, 27, 1113–1127. [Google Scholar] [CrossRef]
- Bredenkamp, N.; Seoighe, C.; Illing, N. Comparative evolutionary analysis of the FoxG1 transcription factor from diverse vertebrates identifies conserved recognition sites for microRNA regulation. Dev. Genes Evol. 2007, 217, 227–233. [Google Scholar] [CrossRef]
- Onorati, M.; Castiglioni, V.; Biasci, D.; Cesana, E.; Menon, R.; Vuono, R.; Talpo, F.; Laguna Goya, R.; Lyons, P.A.; Bulfamante, G.P.; et al. Molecular and functional definition of the developing human striatum. Nat. Neurosci. 2014, 17, 1804–1815. [Google Scholar] [CrossRef]
- Tao, W.; Lai, E. Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain. Neuron 1992, 8, 957–966. [Google Scholar] [CrossRef]
- Shimamura, K.; Rubenstein, J.L. Inductive interactions direct early regionalization of the mouse forebrain. Development 1997, 124, 2709–2718. [Google Scholar]
- Zhao, X.F.; Suh, C.S.; Prat, C.R.; Ellingsen, S.; Fjose, A. Distinct expression of two foxg1 paralogues in zebrafish. Gene Expr. Patterns Gep. 2009, 9, 266–272. [Google Scholar] [CrossRef]
- Pratt, T.; Tian, N.M.; Simpson, T.I.; Mason, J.O.; Price, D.J. The winged helix transcription factor Foxg1 facilitates retinal ganglion cell axon crossing of the ventral midline in the mouse. Development 2004, 131, 3773–3784. [Google Scholar] [CrossRef] [Green Version]
- Tian, N.M.; Pratt, T.; Price, D.J. Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity. Development 2008, 135, 4081–4089. [Google Scholar] [CrossRef] [Green Version]
- Muzio, L.; Mallamaci, A. Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium. J. Neurosci. 2005, 25, 4435–4441. [Google Scholar] [CrossRef]
- Hanashima, C.; Li, S.C.; Shen, L.; Lai, E.; Fishell, G. Foxg1 suppresses early cortical cell fate. Science 2004, 303, 56–59. [Google Scholar] [CrossRef]
- Martynoga, B.; Morrison, H.; Price, D.J.; Mason, J.O. Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis. Dev. Biol. 2005, 283, 113–127. [Google Scholar] [CrossRef] [Green Version]
- Miyoshi, G.; Fishell, G. Dynamic FoxG1 expression coordinates the integration of multipolar pyramidal neuron precursors into the cortical plate. Neuron 2012, 74, 1045–1058. [Google Scholar] [CrossRef]
- Toma, K.; Kumamoto, T.; Hanashima, C. The timing of upper-layer neurogenesis is conferred by sequential derepression and negative feedback from deep-layer neurons. J. Neurosci. 2014, 34, 13259–13276. [Google Scholar] [CrossRef]
- Smith, R.; Huang, Y.T.; Tian, T.; Vojtasova, D.; Mesalles-Naranjo, O.; Pollard, S.M.; Pratt, T.; Price, D.J.; Fotaki, V. The Transcription Factor Foxg1 Promotes Optic Fissure Closure in the Mouse by Suppressing Wnt8b in the Nasal Optic Stalk. J. Neurosci. 2017, 37, 7975–7993. [Google Scholar] [CrossRef]
- Pauley, S.; Lai, E.; Fritzsch, B. Foxg1 is required for morphogenesis and histogenesis of the mammalian inner ear. Dev. Dyn. 2006, 235, 2470–2482. [Google Scholar] [CrossRef] [Green Version]
- Duggan, C.D.; DeMaria, S.; Baudhuin, A.; Stafford, D.; Ngai, J. Foxg1 is required for development of the vertebrate olfactory system. J. Neurosci. 2008, 28, 5229–5239. [Google Scholar] [CrossRef]
- Xuan, S.; Baptista, C.A.; Balas, G.; Tao, W.; Soares, V.C.; Lai, E. Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres. Neuron 1995, 14, 1141–1152. [Google Scholar] [CrossRef] [Green Version]
- Ryu, K.; Yokoyama, M.; Yamashita, M.; Hirano, T. Induction of excitatory and inhibitory presynaptic differentiation by GluD1. Biochem. Biophys. Res. Commun. 2012, 417, 157–161. [Google Scholar] [CrossRef]
- Livide, G.; Patriarchi, T.; Amenduni, M.; Amabile, S.; Yasui, D.; Calcagno, E.; Lo Rizzo, C.; De Falco, G.; Ulivieri, C.; Ariani, F.; et al. GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. Eur. J. Hum. Genet. 2015, 23, 195–201. [Google Scholar] [CrossRef]
- Martínez-Cerdeño, V. Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models. Dev. Neurobiol. 2017, 77, 393–404. [Google Scholar] [CrossRef]
- Xu, X.; Miller, E.C.; Pozzo-Miller, L. Dendritic spine dysgenesis in Rett syndrome. Front. Neuroanat. 2014, 8, 97. [Google Scholar] [CrossRef]
Clinical Features | Deletion/Intragenic Mutations of FOXG1 | Duplication of FOXG1 |
---|---|---|
Neurodevelopment | Severe global delay | Global delay, but variable severities |
Speech | Absence or minimal | Delay, but may produce beyond words |
Ambulation | Typically not acquired | Impaired, but may have ability to walk |
Social contact | Impaired | Impaired |
Sleep disorder | Present | Present |
Visual impairment | High-level visual dysfunctions, strabismus, small optic disc, etc. | +/− |
Breathing abnormalities | +/− | +/− |
Movement disorder: Dyskinesia, hyperkinetic movements | Starts from early childhood | +/− |
Stereotypies | Present | +/− |
Microcephaly | Typically normal or borderline small at birth, evolving to severe microcephaly in infancy | +/− |
Brain MRI | Corpus callosum hypogenesis/agenesis; forebrain anomaly; delayed myelination | Typically normal |
Epilepsy | Onset in early childhood, variable seizure types, often refractory to treatment | Infantile spasms, mostly responsive to adrenocorticotropic hormone (ACTH) |
Reference | Sex | Genomic Locus/Coordinates (Genomic Mapping Reference) | Size (Mb) | Inheritance |
---|---|---|---|---|
[17] | F | Chr 14: 25.97–30.42 Mb (hg18) | 4.45 | De novo |
[18] | M | Chr 14: 26908812–30254928 (hg18) | 3.3–3.4 | De novo |
F | Chr 14: 19582682–29076500 (hg18) | 9.4–11 | De novo | |
M | Chr 3: 191656626–199287624 Chr 14: 19582682–33275612 (hg18) | 7.6–8.4 13.7–18.4 | Mother: Chr 3; 14 translocation | |
M | Chr 14: 28217364–34635622 (hg18) | 6.4 | De novo | |
M | Chr 14: 27474978–30603041 (hg18) | 3.1 | De novo | |
M | Chr 14: 19508845–34063670 (hg18) | 14.5 | De novo | |
M | Chr 14: 28257153–35048345 (hg18) | 6.8 | N/A | |
[19] | F | Chr 14: 27165797–30192375 (hg18) | 3.3 | De novo |
[20] | M | Chr14: 19.365Kb–30.359Kb (hg18) | 11 | Small extranumerary marker (with part of duplication) from maternal balanced translocation involving chr 14 and 15. |
M | Chr 14: 27409kb-30603kb (hg18) | 3.2 | De novo | |
[21] | F | Chr14: 19761035–30941609, Mosaic duplication (N/A) | 11.1 | Maternal uniparental disomy 14 and mosaic small marker of paternal origin containing the proximal long arm of chr 14. |
[12] | M | Chr 14: 26169335–30237575 (hg18) | 4.1 | De novo |
M | Chr 14: 19528022–35193884 (hg18) | 15.6 | De novo | |
M | Chr 14: 21927637–55833232 (hg18) | 33.9 | De novo | |
M | Chr 14: 20555119–33885364 (hg18) | 13.3 | De novo | |
F | Chr 14: 26558014–30980441 (hg19) | 4.4 | De novo | |
[23] | F | Chr 14: 19365051–31212370 (hg18) | 11.84 | De novo |
[4] | M | Chr14: 19043189–33814746 (N/A) | 14.8 | De novo |
[63] | F | Chr14: 20516277–38826881 (hg17) | 18.3 | De novo |
[25] | F | Chr14: 20203610–40396835 (hg19) | 20 | De novo |
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Wong, L.-C.; Singh, S.; Wang, H.-P.; Hsu, C.-J.; Hu, S.-C.; Lee, W.-T. FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms. Int. J. Mol. Sci. 2019, 20, 4176. https://doi.org/10.3390/ijms20174176
Wong L-C, Singh S, Wang H-P, Hsu C-J, Hu S-C, Lee W-T. FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms. International Journal of Molecular Sciences. 2019; 20(17):4176. https://doi.org/10.3390/ijms20174176
Chicago/Turabian StyleWong, Lee-Chin, Shekhar Singh, Hsin-Pei Wang, Chia-Jui Hsu, Su-Ching Hu, and Wang-Tso Lee. 2019. "FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms" International Journal of Molecular Sciences 20, no. 17: 4176. https://doi.org/10.3390/ijms20174176