The Forkhead/Winged Helix Gene Mf1 Is Disrupted in the Pleiotropic Mouse Mutation congenital hydrocephalus

Kume, Tsutomu; Deng, Ke Yu; Winfrey, Virginia P.; Gould, Douglas B.; Walter, Michael A.; Hogan, Brigid L.M.

doi:10.1016/s0092-8674(00)81204-0

Cited by 356 publications

(401 citation statements)

References 52 publications

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“…62 Most homozygous null mutants of Foxc1, generated either from a targeted allele (Foxc1 À/À ) or the spontaneous mutation congenital hydrocephalus (Foxc1 ch/ch ) die preand perinatally with hemorrhagic hydrocephalus and severe skeletal, cardiovascular and ocular defects. 63 The heterozygote Foxc1 þ /À and Foxc1 ch/ þ mice have anterior segment abnormalities similar to those observed in patients. These include eccentric and irregularly shaped pupils, iris hypoplasia, displaced Schwalbe's line and abnormal aqueous humor drainage structures, but IOP is not elevated.…”

Section: Phenotypic Features Of Foxc1 and Pitx2 Knockout Micementioning

confidence: 63%

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

2009

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In association withAxenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations Axenfeld -Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations.

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Section: Phenotypic Features Of Foxc1 and Pitx2 Knockout Micementioning

confidence: 63%

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

2009

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“…[11][12][13][14][15] Homozygous null mutations of Mf1, the murine homologue of FKHL7, have been shown to be responsible for the congenital hydrocephalus (ch) phenotype in mice. 16 These results suggest that FKHL7 has a key role in the development of the mammalian eye and brain.…”

Section: Introductionmentioning

confidence: 92%

Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25

et al. 2000

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Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.

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“…Consistent with its expression in developing paraxial mesoderm, prechondrogenic and periocular mesenchyme, the meninges, cardiovascular system, and kidney, Foxc1 null mice die at birth with hydrocephalus, multiple skeletal abnormalities, renal, cardiovascular, and eye defects. 2 In keeping with this, humans with FOXC1 haploinsufficiency, through mutation or deletion, exhibit the Axenfeld-Rieger syndrome characterized by developmental defects of the anterior chamber of the eye and glaucoma, as well as other dental, skeletal, and cardiac abnormalities. 3 FOXC1 loss also results in the DandyWalker malformation, characterized by cerebellar hypoplasia and an enlarged posterior fossa.…”

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confidence: 90%