Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome

Semina, Elena V.; Reiter, Rebecca S.; Leysens, Nancy J.; Alward, Wallace L.M.; Small, Kent W.; Datson, Nicole A.; Siegel‐Bartelt, J.; Bierke-Nelson, D.; Bitoun, Pierre; Zabel, Bernhard; Carey, John C.; Murray, Jeffrey C.

doi:10.1038/ng1296-392

Cited by 825 publications

(713 citation statements)

References 57 publications

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“…This motif was suggested to trigger DNA binding and transactivation. 10 Thus, the mutation is highly likely to be pathogenic and thus supports a role for PITX1 in complex lower-limb malformation.…”

Section: Resultsmentioning

confidence: 77%

Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly

Klopocki

Kähler²,

Foulds

et al. 2012

Eur J Hum Genet

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PITX1 is a bicoid-related homeodomain transcription factor implicated in vertebrate hindlimb development. Recently, mutations in PITX1 have been associated with autosomal-dominant clubfoot. In addition, one affected individual showed a polydactyly and right-sided tibial hemimelia. We now report on PITX1 deletions in two fetuses with a high-degree polydactyly, that is, mirror-image polydactyly. Analysis of DNA from additional individuals with isolated lower-limb malformations and higher-degree polydactyly identified a third individual with long-bone deficiency and preaxial polydactyly harboring a heterozygous 35 bp deletion in PITX1. The findings demonstrate that mutations in PITX1 can cause a broad spectrum of isolated lower-limb malformations including clubfoot, deficiency of long bones, and mirror-image polydactyly.

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Section: Resultsmentioning

confidence: 77%

Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly

Klopocki

Kähler²,

Foulds

et al. 2012

Eur J Hum Genet

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“…Mutations in PITX2, a member of the PITX/RIEG family of bicoid-related homeobox genes, are responsible for the autosomal-dominant disorder Rieger syndrome, which exhibits defects in the tooth and eye (Semina et al, 1996). In mice, Pitx2 is expressed in the presumptive dental epithelium before tooth formation and is continued in the dental epithelium throughout the entire tooth developmental process (St. Amand et al, 2000;Fig.…”

Section: Mouse and Human Exhibit Similar Expression Pattern Of Pitx2 mentioning

confidence: 99%

“…Knockout of Msx1, Pax9, or Pitx2 in mice causes failed tooth development (Satakata and Maas, 1994;Peters et al, 1998;Lin et al, 1999;Lu et al, 1999). In humans, mutations in each of these genes are also associated with tooth phenotypes, including tooth agenesis and oligodontia (Semina et al, 1996;Vastardis et al, 1996;Van den Boogaard et al, 2000;Lidral and Reising, 2002;Stockton et al, 2002).…”

Section: Expression Of Fgf8 Pax9 and Shox2 In Developing Human Tootmentioning

confidence: 99%

Expression survey of genes critical for tooth development in the human embryonic tooth germ

Lin

Huang

et al. 2007

Developmental Dynamics

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In the developing murine tooth, the expression patterns of numerous regulatory genes have been examined and their roles have begun to be revealed. To unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of several regulatory genes, including BMP4, FGF8, MSX1, PAX9, PITX2, and SHOX2, and compared them with that found in mice. All of these genes are known to play critical roles in murine tooth development. Our results show that these genes exhibit basically similar expression patterns in the human tooth germ compared with that in the mouse. However, slightly different expression patterns were also observed for some of the genes at certain stages. For example, MSX1 expression was detected in the inner enamel epithelium in addition to the dental mesenchyme at the bell stage of the human tooth. Moreover, FGF8 expression remained in the dental epithelium at the cap stage, while PAX9 and SHOX2 expression was detected in both dental epithelium and mesenchyme of the human tooth germ. Our results indicate that, although slight differences exist in the gene expression patterns, the human and mouse teeth not only share considerable homology in odontogenesis but also use similar underlying molecular networks. Developmental Dynamics 236:1307-1312, 2007.

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“…About 80 years after it was first described, Elena Semina et al characterised the first gene mutations causing dominantly inherited Rieger syndrome in the PITX2 gene on chromosome 4q25. 4 However, mutations in the PITX2 gene are not the sole cause of ASD; at least four other gene loci have been identified on 6p25, 13q14 and 16q24, and 11p13. [5][6][7] The genes FOXC1 and PAX6 at 6p25, and 11p13 respectively have been identified, 8,9 but the others remain elusive.…”

Section: Classification Of Asdmentioning

confidence: 99%

“…One intriguing disease feature is that patients with PITX2 mutation often present with abnormal belly buttons, due to a failure of involution of the pre-umbilical skin post-natally. 4,15 In mouse models that completely lack Pitx2 function there is failure to close the ventral body wall of the embryo leaving the heart and abdominal organs exposed, 19 and this seems to represent the severe end of a malformation spectrum ranging to the mild umbilical phenotype seen in patients with heterozygous mutations.…”

Section: Expression Of Asd Genesmentioning

confidence: 99%

Molecular and developmental mechanisms of anterior segment dysgenesis

Sowden

2007

Eye

136

102

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Anterior segment dysgenesis (ASD) is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma and corneal opacity. Several different gene mutations have been identified underlying these anomalies with the majority of ASD genes encoding transcriptional regulators. In this review, the role of the ASD genes, PITX2 and FOXC1, is considered in relation to the embryology of the anterior segment, the biochemical function of these proteins, and their role in development and disease aetiology. The emerging view is that these genes act in concert to specify a population of mesenchymal progenitor cells, mainly of neural crest origin, as they migrate anteriorly around the embryonic optic cup. These same genes then regulate mesenchymal cell differentiation to give rise to distinct anterior segment tissues. Development appears critically sensitive to gene dosage, and variation in the normal level of transcription factor activity causes a range of anterior segment anomalies. Interplay between PITX2 and FOXC1 in the development of different anterior segment tissues may partly explain the phenotypic variability and the genetic heterogeneity characteristic of ASD.

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Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome

Cited by 825 publications

References 57 publications

Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly

Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly

Expression survey of genes critical for tooth development in the human embryonic tooth germ

Molecular and developmental mechanisms of anterior segment dysgenesis

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