GTF2IRD1 in Craniofacial Development of Humans and Mice

Tassabehji, May; Hammond, Peter; Karmiloff‐Smith, Annette; Thompson, Pamela; Thorgeirsson, Snorri S.; Durkin, Marian E.; Popescu, Nicholas C.; Hutton, Timothy; Metcalfe, Kay; Rucka, A; Stewart, Helen; Read, Andrew P.; Maconochie, Mark

doi:10.1126/science.1116142

Cited by 188 publications

(216 citation statements)

References 22 publications

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“…This is consistent with the expression pattern of Gtf2ird1 in the development of the brain and craniofacial areas. Furthermore, this conclusion is supported by the function of GTF2IRD1 to regulate expression of genes, which are involved in craniofacial and skeletal development [184]. Furthermore, mutant mice reveal reduced fear and aggression and increased social behaviour, which would be in accord with the typical findings of hypersociability in WBS.…”

Section: The Single Copy Gene Part Of the Wbs Regionmentioning

confidence: 58%

The genomic basis of the Williams – Beuren syndrome

Schubert

2008

Cell. Mol. Life Sci.

214

161

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. The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects.

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Section: The Single Copy Gene Part Of the Wbs Regionmentioning

confidence: 58%

The genomic basis of the Williams – Beuren syndrome

Schubert

2008

Cell. Mol. Life Sci.

214

161

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“…On the contrary, no differences in cranial morphology were reported in mice lacking the human distal region (Limk1:Gtf2i), in contrast to reported cases of individuals with atypical deletions that postulate a role for the most WBSCR distal genes as involved in the craniofacial phenotype. 2,3,22,29 Overall, these results highlight the complexity of craniofacial development and WBS.…”

Section: Patient Wbs166mentioning

confidence: 76%

“…22 In addition, GTF2IRD1 regulates the goosecoid gene involved in craniofacial morphogenesis 23 as well, as mice haploinsuficient for a mouse model carrying a deletion between Clip2 and Gtf2ird1 show hypoplasia of the mandible and other craniofacial defects resembling the defects and dental problems of WBS individuals. 24 However, another targeted knockout of Gtf2ird1 failed to find craniofacial dysmorphology, 25 suggesting RHBDD2 HAG GTF2IRD1 GTF2I HIP1 CALN1 CCL26 CCL24 CCL24 POR TMPIT STYXL1 MDH2 HSPB1 YW SRCRB4D ZP3 MAGI2 BAZ1B BCL7B TBL2 WBSCR14 WBSCR24 WBSCR18 WBSCR22 WBSCR26 WBSCR21 WBSCR27 WBSCR28 WBSCR1 WBSCR5 WBSCR23 STX1A CLDN4 CLDN3 ELN LIMK1 RFC2 CLIP2 TRIM50 FKBP6 Atypical patients in Williams Beuren syndrome C Fusco et al that this phenotype may be influenced by different genetic background of diverse strains.…”

Section: Patient Wbs166mentioning

confidence: 99%

Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits

et al. 2013

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syndrome (WBS) is a multisystemic disorder caused by a hemizygous deletion of 1.5 Mb on chromosome 7q11.23 spanning 28 genes. A few patients with larger and smaller WBS deletion have been reported. They show clinical features that vary between isolated SVAS to the full spectrum of WBS phenotype, associated with epilepsy or autism spectrum behavior. Here we describe four patients with atypical WBS 7q11.23 deletions. Two carry B3.5 Mb larger deletion towards the telomere that includes Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxigenase activation protein gamma (YWHAG) genes. Other two carry a shorter deletion of B1.2 Mb at centromeric side that excludes the distal WBS genes BAZ1B and FZD9. Along with previously reported cases, genotype-phenotype correlation in the patients described here further suggests that haploinsufficiency of HIP1 and YWHAG might cause the severe neurological and neuropsychological deficits including epilepsy and autistic traits, and that the preservation of BAZ1B and FZD9 genes may be related to mild facial features and moderate neuropsychological deficits. This report highlights the importance to characterize additional patients with 7q11.23 atypical deletions comparing neuropsychological and clinical features between these individuals to shed light on the pathogenic role of genes within and flanking the WBS region.

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“…1,2 Using highly sensitive models of facial morphology, it has been possible to detect subtle differences in atypical patients and inform genotype-phenotype studies. 3,4 Advanced molecular genetic techniques have established increasingly detailed correlations between genotype and phenotype. It has been the subject of debate whether it is valid to distinguish ethnic or ancestral categories in such studies.…”

Section: Introductionmentioning

confidence: 99%

Face shape differs in phylogenetically related populations

Hopman

Merks

Suttie³

et al. 2014

Eur J Hum Genet

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3D analysis of facial morphology has delineated facial phenotypes in many medical conditions and detected fine grained differences between typical and atypical patients to inform genotype-phenotype studies. Next-generation sequencing techniques have enabled extremely detailed genotype-phenotype correlative analysis. Such comparisons typically employ control groups matched for age, sex and ethnicity and the distinction between ethnic categories in genotype-phenotype studies has been widely debated. The phylogenetic tree based on genetic polymorphism studies divides the world population into nine subpopulations. Here we show statistically significant face shape differences between two European Caucasian populations of close phylogenetic and geographic proximity from the UK and The Netherlands. The average face shape differences between the Dutch and UK cohorts were visualised in dynamic morphs and signature heat maps, and quantified for their statistical significance using both conventional anthropometry and state of the art dense surface modelling techniques. Our results demonstrate significant differences between Dutch and UK face shape. Other studies have shown that genetic variants influence normal facial variation. Thus, face shape difference between populations could reflect underlying genetic difference. This should be taken into account in genotype-phenotype studies and we recommend that in those studies reference groups be established in the same population as the individuals who form the subject of the study.

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GTF2IRD1 in Craniofacial Development of Humans and Mice

Cited by 188 publications

References 22 publications

The genomic basis of the Williams – Beuren syndrome

The genomic basis of the Williams – Beuren syndrome

Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits

Face shape differs in phylogenetically related populations

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