Mutations in BMP4 Are Associated with Subepithelial, Microform, and Overt Cleft Lip

Suzuki, Satoshi; Marazita, Mary L.; Cooper, Margaret E.; Miwa, Noriko; Hing, Anne V.; Jugessur, Astanand; Natsume, Nagato; Shimozato, Kazuo; Ohbayashi, Naofumi; Suzuki, Yasushi; Niimi, Teruyuki; Minami, Kazumasa; Yamamoto, Masahiko; Altannamar, Tserendorj J.; Erkhembaatar, Tudevdorj; Furukawa, Hiroyuki; Daack-Hirsch, Sandra; L'Heureux, Jamie; Brandon, Carla A.; Weinberg, Seth M.; Neiswanger, Katherine; Deleyiannis, Frederic W.‐B.; Salamanca, Javier; Vieira, Alexandre R.; Lidral, Andrew C.; Martin, James F.; Murray, Jeffrey C.

doi:10.1016/j.ajhg.2009.02.002

Cited by 184 publications

(190 citation statements)

References 32 publications

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“…Normal variation at or near the time of fusion underestimates potential variation, as evidenced by the large number of genes known to contribute to primary cleft incidence and severity in humans (Dixon et al, 2011), many of which modulate the growth of prominences (Suzuki et al, 2009;Suazo et al, 2011). We targeted SHH signaling because of its known role in controlling mesenchymal growth zones,…”

Section: Resultsmentioning

confidence: 99%

Embryonic bauplans and the developmental origins of facial diversity and constraint

et al. 2014

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A central issue in biology concerns the presence, timing and nature of phylotypic periods of development, but whether, when and why species exhibit conserved morphologies remains unresolved. Here, we construct a developmental morphospace to show that amniote faces share a period of reduced shape variance and convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict in silico the phenotypic outcomes of unoccupied morphospaces and experimentally validate in vivo that observed convergence is not due to developmental limits on variation but instead from selection against novel trajectories that result in maladaptive facial clefts. These results illustrate how epigenetic factors such as organismal geometry and shape impact facial morphogenesis and alter the locus of adaptive selection to variation in later developmental events.

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Section: Resultsmentioning

confidence: 99%

Embryonic bauplans and the developmental origins of facial diversity and constraint

et al. 2014

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“…The nucleotide variant rs227731 is located 100kb centromeric of the NOG gene. NOG acts as antagonist of members of the TGF-b superfamily, which have been implicated in orofacial clefting 35 . Recently, Leslie et al 36 identified a common causative variant rs227727 near the NOG gene, which leads to disruption of its enhancer activity.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the most common orofacial birth defect with an aetiology involving both genetic and environmental factors. Genome-wide association studies (GWAS) have identified several genomic susceptibility regions for nsCL/P. In the present study, the three well established single nucleotide polymorphisms (SNPs) identified by GWAS (rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were analysed for an association with nsCL/P in Slovak population. Methods. Nucleotide variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All variants of interest were genotyped using high-resolution melting analysis after real-time PCR. Results. We found significant differences between patient and control groups with respect to the allele and genotype frequencies for the SNPs at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward association with nsCL/P risk. Conclusions.The results suggest that SNPs at the 1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.

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“…Mutations in components of the FGF and BMP signaling pathways have been shown to result in severe facial defects including cleft lip and cleft palate in humans and mice (Trumpp et al, 1999;Trokovic et al, 2003;Liu et al, 2005;Riley et al, 2007;Suzuki et al, 2009). Tbx22 is induced by FGF and inhibited by BMP signaling, raising the question, which roles of these pathways it may mediate.…”

Section: Functions Of Tbx22 Downstream Of Fgf and Bmp Signaling In Dementioning

confidence: 99%

Regulation of Tbx22 during facial and palatal development

Fuchs

Inthal

Herrmann

et al. 2010

Developmental Dynamics

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Mutations in the gene encoding the T-box transcription factor TBX22 cause X-linked cleft palate and ankyloglossia in humans. Here we show that Tbx22 expression during facial and palatal development is regulated by FGF and BMP signaling. Our results demonstrate that FGF8 induces Tbx22 in the early face while BMP4 represses and thus restricts its expression. This regulation is conserved between chicken and mouse, although the Tbx22-expression patterns differ considerably between these two species. We suggest that these species-specific differences may result at least in part from differences in the spatiotemporal patterns of BMP activity, but we exclude a direct repression of Tbx22 by the BMP-inducible transcriptional repressor MSX1. Together these findings help to integrate Tbx22 into the molecular network of factors regulating facial development. Developmental Dynamics 239:2860-2874,

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Mutations in BMP4 Are Associated with Subepithelial, Microform, and Overt Cleft Lip

Cited by 184 publications

References 32 publications

Embryonic bauplans and the developmental origins of facial diversity and constraint

Embryonic bauplans and the developmental origins of facial diversity and constraint

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Regulation of Tbx22 during facial and palatal development

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