Mutations in the Human TBX4 Gene Cause Small Patella Syndrome

Bongers, Ernie M.H.F.; Duijf, Pascal H.G.; Beersum, Sylvia E.M. van; Schoots, Jeroen; Kampen, A. van; Burckhardt, A; Hamel, B.C.J.; Losan, F; Hoefsloot, Lies H.; Yntema, Helger G.; Knoers, Nine V A M; Bokhoven, Hans van

doi:10.1086/421331

Cited by 155 publications

(156 citation statements)

References 36 publications

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“…147891) and Holt-Oram syndrome (HOS; OMIM no. 142900), respectively (Basson et al, 1997;Li et al, 1997;Bongers et al, 2004). HOS is a dominant disorder affecting the heart and upper limbs.…”

Section: Tbx Genes Establish the Fgf Signalling Loop In The Nascent Lmentioning

confidence: 99%

Regulation of limb bud initiation and limb‐type morphology

Duboc¹,

Logan²

2011

Developmental Dynamics

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While the paired forelimb and hindlimb buds of vertebrates are initially morphologically homogeneous, as the limb progenitors differentiate, each individual tissue element attains a characteristic limb-type morphology that ultimately defines the constitution of the forelimb or hindlimb. This review focuses on contemporary understanding of the regulation of limb bud initiation and formation of limb-type specific morphologies and how these regulatory mechanisms evolved in vertebrates. We also attempt to clarify the definition of the terms limb-type identity and limb-type morphology that have frequently been used interchangeably. Over the last decade, three genes, Tbx4, Tbx5, and Pitx1, have been extensively studied for their roles in limb initiation and determining limb-type morphologies. The role of Tbx4 and Tbx5 in limb initiation is clearly established. However, their putative role in the generation of limb-type morphologies remains controversial. In contrast, all evidence supports a function for Pitx1 in determination of hindlimb morphologies.

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Section: Tbx Genes Establish the Fgf Signalling Loop In The Nascent Lmentioning

confidence: 99%

Regulation of limb bud initiation and limb‐type morphology

Duboc¹,

Logan²

2011

Developmental Dynamics

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“…Because these differences were already clear at E11.5 and ablation of Tbx4 after E11.5 led to no additional phenotype, the early loss of limb core tissue was almost certainly the origin of the skeletal malformations observed at E14.5. This suggests that the limb malformations seen in human heterozygous mutations of TBX4 (Bongers et al, 2004), which cause mild malformation of pelvis, patella size and toe placement (Small Pateela Syndrome, OMIM 147891), are determined in early development rather than during later limb outgrowth. Gene ablation and lineage tracing has shown that digit I is Shhindependent, and digit II is induced by neighboring Shh signaling, while digits III, IV and V arise from tissue that once expressed Shh (Harfe et al, 2004).…”

Section: Hindlimb Formation Requirements For Tbx4mentioning

confidence: 99%

“…Several T-box genes are expressed in the limb (Naiche et al, 2005), and heterozygous mutations in TBX3, TBX4 and TBX5 cause limb defects in humans (Bamshad et al, 1997;Basson et al, 1997;Bongers et al, 2004). In mouse, all of the Tbx2 subfamily (Tbx2, Tbx3, Tbx4 and Tbx5) have been shown to play roles in limb development (Agarwal et al, 2003;Davenport et al, 2003;Harrelson et al, 2004;Naiche and Papaioannou, 2003).…”

Section: Introductionmentioning

confidence: 99%

Tbx4is not required for hindlimb identity or post-bud hindlimb outgrowth

Naiche

Papaioannou

2007

Development

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Tbx4 is a crucial gene in the initiation of hindlimb development and has been reported as a determinant of hindlimb identity and a presumptive direct regulator of Fgf10 in the limb. Using a conditional allele of Tbx4, we have ablated Tbx4 function before and after limb initiation. Ablation of Tbx4 before expression in the hindlimb field confirms its requirement for limb bud outgrowth. However, ablation of Tbx4 shortly after onset of expression in the hindlimb field, during limb bud formation, alters neither limb outgrowth nor expression of Fgf10. Instead, post-limb-initiation loss of Tbx4 results in reduction of limb core tissue and hypoplasia of proximal skeletal elements. Loss of Tbx4 during later limb outgrowth produces no limb defects, revealing a brief developmental requirement for Tbx4 function. Despite evidence from ectopic expression studies, our work establishes that loss of Tbx4 has no effect on hindlimb identity as assessed by morphology or molecular markers.

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“…Küçük patella sendromu otozomal dominant geçişli bir sorundur. [21] Patellar hipoplazi veya aplazi, iskiyopubik birleşkenin iki taraflı gecikmiş veya oluşmamış ossifikasyon merkezi ve infra-asetabuler balta şekilli çentikler ile karakterizedir (Şekil 3). Küçük patella sendromuna 1. ve 2. ayak parmak arasının normalden geniş olması, ayakta kısa 4. ve 5. metatarsal kemikler ve pes planus eşlik edebilir.…”

Section: Küçük Patella Sendromuunclassified

“…Bazı olgularda ise, talus boynunda hipertrofi, tarsal koalisyon, skapulanın anormal şekli, kısa 4. ve 5. metakarplar, koksa vara veya valga, genu valgum, dar ve uzun femur boyunları ve hipoplastik trokanter minörler bildirilmiştir. [20,21] …”

Section: Küçük Patella Sendromuunclassified

Congenital patellofemoral joint problems

Şahin¹

2012

TOTBİD Dergisi

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Doğuştan patellofemoral patolojiler, hem anatomik olarak normal gelişimini tamamlamış, hem de displastik gelişim göstermiş dizlerde görülebilir. Patellanın doğuştan çıkığı, doğum esnasında var olan ve ekstansör mekanizmanın tam olarak işlev görmesine engel olan bir bozukluktur. Doğuştan patella çıkığının, sekonder kemik deformiteleri gelişmeden önce erken dönemde tedavi edilmesi büyük önem taşımaktadır. Patellofemoral eklemin nadir görülen doğuştan sorunlarından biri de, ekstansör mekanizma duplikasyonudur. Tedavisinde hipoplastik olan yapı kesilir ve geride kalan baskın ekstansör mekanizma, santralize edilerek işlevsel bir hale getirilir. Tırnak patella sendromu genellikle patello femoral tutulum ile kendini gösteren bir diğer genetik bozukluktur. Hastalık, tırnaklarda bozukluklar, radius başı hipoplazisi veya tamamen yokluğu, posteriyor iliyak çıkıntılar üstünde veya kenarında iliyak boynuzların gelişmesi ile karakterizedir. Down sendromuna bağlı patellar instabilite ve çok parçalı patella kırıkları da, diğer patellofemoral bozuklar arasında sayılabilir. Özellikle patellanın superiyor ve lateral kadranında görülen çoklu ossifikasyon merkezleri sık karşılaşılan bir durumdur.

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Mutations in the Human TBX4 Gene Cause Small Patella Syndrome

Cited by 155 publications

References 36 publications

Regulation of limb bud initiation and limb‐type morphology

Regulation of limb bud initiation and limb‐type morphology

Tbx4is not required for hindlimb identity or post-bud hindlimb outgrowth

Congenital patellofemoral joint problems

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