Sequence evaluation of FGF and FGFR gene conserved non‐coding elements in non‐syndromic cleft lip and palate cases

Riley, Bridget; Murray, Jeffrey C.

doi:10.1002/ajmg.a.31965

Cited by 49 publications

(51 citation statements)

References 26 publications

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“…8 Mutations in FGFR1 , a gene involved in olfactory bulb morphogenesis, 9,10 have been identified in Kallmann syndrome cases 11 as well as cases of nonsyndromic clefting. 12,13 Using structural MRI, individuals with nonsyndromic orofacial clefts have also been shown display significant volumetric reductions in the orbitofrontal cortex, 14 a portion of the ventral prefrontal cortex shown to have an important role in olfactory processing. 15 …”

Section: Introductionmentioning

confidence: 99%

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting

May

Sanchez

Deleyiannis

et al. 2015

Journal of Craniofacial Surgery

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Improved understanding of the phenotypic spectrum associated with nonsyndromic orofacial clefting (OFC) has the potential to inform efforts to uncover the etiology of this complex trait. Prior studies report that individuals with OFC are characterized by impaired olfactory ability. In this study we test whether olfactory dysfunction extends to the unaffected parents of children with OFC. The University of Pennsylvania Smell Identification Test (UPSIT) was used to measure olfactory ability in a sample of 60 unaffected mothers and fathers with cleft-affected children. The proportion of deficit was compared to reference data obtained from published sex-and age-specific norms on over 2700 individuals. The proportion of deficit was significantly higher in unaffected parents compared with baseline controls (41.7% versus 12.6%; p<0.001). 41.7% of unaffected fathers displayed evidence of deficit compared with 15.1% of male controls (p=0.001), while 41.7% of mothers exhibited deficits compared with 10.4% of female controls (p<0.001). Olfactory deficits are present at a high proportion in the unaffected parents of individuals with OFC. This suggests that the deficits observed in affected cases may not simply be a secondary consequence of surgical repair, and may instead be an informative phenotype reflecting underlying etiology.

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Section: Introductionmentioning

confidence: 99%

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting

May

Sanchez

Deleyiannis

et al. 2015

Journal of Craniofacial Surgery

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“…In the past few years, great efforts have been taken to unravel genetic background leading to its pathogenesis [Grant et al, 2009]. Several potentially causal genes have been identified, such as IRF6 [Zucchero et al, 2004], MSX1 [Van den Boogaard et al, 2008], TGFB3 [Reutter et al, 2008], TGFA , PDGFC [Choi et al, 2009], PVRL1 [Avila et al, 2006], FGFs [Riley and Murray, 2007], TBX22 [Pauws et al, 2009], among which the interferon regulatory factor 6, IRF6 on chr. 1q32, has the most supporting data.…”

Section: Introductionmentioning

confidence: 99%

IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese Han population

Pan

Zhang

et al. 2010

American J of Med Genetics Pt A

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IRF6 plays an important role in orofacial development. In the present study, we genotyped two polymorphisms (rs642961 and rs2235371) within the IRF6 locus and estimated their associations with risk of nonsyndromic orofacial clefts (NSOC), including the subgroups, in a hospital-based case-control study in a Chinese Han population. In the single locus analyses, we found rs642961 AG and AG/AA genotypes were associated with increased risk of NSOC, especially cleft lip with or without cleft palate (CL/P) and cleft lip with cleft palate (CLP), while significantly decreased risks were associated with rs2235371 CT and CT/TT genotypes. When examining the combined effects of these two polymorphisms and using the rs642961 A and rs2235371 C alleles as the risk alleles, we found genotypes containing 2-4 risk alleles conferred high risk to NSOC, CL/P, and CLP. Furthermore, to test whether rs642961 could modulate IRF6 expression in vivo, we surgically collected lip skin tissues within the adjacent region of lip cleft site and found rs642961 genotypes were associated with differential levels of IRF6 mRNA and protein expression in an allele-dosage manner, providing the first evidence that rs642961 affected IRF6 expression in vivo. Taken together, these findings confirm the contribution of IRF6 genetic variants in the etiology of NSOC in a Chinese Han population.

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“…Approximately 20% of Kallmann syndrome cases a loss-of-function mutation in FGFR1 has been reported [26]. Recent analysis has shown 3 to 5% of nonsyndromic cleft lip or palate is also caused by functional impairment in the FGFR1, FGFR2, FGFR3, and FGF8 genes [27]. Cleft lip/palate ectodermal dysplasia syndrome (CLPED) is an autosomal recessive disorder is also characterised by cleft lip with or without cleft palate.…”

Section: Insights From Syndromic Cleftsmentioning

confidence: 99%

Molecular Genetics of Non-Syndromic Clefts Revisited

Rajasekhar¹,

Lakkakula²,

KS³

2011

Int J Genet

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Cleft of the lip and palate (CL/P) are generally divided in to two groups, isolated cleft palate and cleft with or without cleft palate representing a heterogeneous group of disorders affecting the upper lip and the roof the mouth. Non-syndromic cleft lip and palate incidence is 1 in 700 to 1000 live babies with ethnic and geographic variations. Various independent association and linkage studies using different populations have identified several loci. Numerous genes have been reported in studies demonstration associations and/or linkage of the cleft lip and palate phenotypes to alleles of microsatellite markers and single nucleotide polymorphisms within specific genes that regulate transcription factor, growth factor, cell signalling and detoxification metabolisms. Currently, efforts are focussed to identify the genes and genetic variations within the numerous candidate genes that have been found to associate with the expression of the orofacial cleft phenotype. In conclusion, the genetic basis of CL/P is still contentious because of genetic complexity of clefting.

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Sequence evaluation of FGF and FGFR gene conserved non‐coding elements in non‐syndromic cleft lip and palate cases

Cited by 49 publications

References 26 publications

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting

IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese Han population

Molecular Genetics of Non-Syndromic Clefts Revisited

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