Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene

Ghassibé, Michella; Revençu, Nicole; Bayet, Bénédicte; Gillerot, Y.; Vanwijck, Romain; Verellen‐Dumoulin, Christine; Vikkula, Miikka

doi:10.1136/jmg.2003.009274

Cited by 54 publications

(68 citation statements)

References 20 publications

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“…13 We could not identify the rare I allele in 110 tested controls from Europe, nor in a set of European individuals with VWS. 12 Based on these two observations, the role of this polymorphism was not investigated in this study, and it is likely not the disease-causing variant.…”

Section: Discussionmentioning

confidence: 99%

“…10 Recently, the interferon regulatory factor-6 (IRF6) gene on 1q32.2 was shown to harbor mutations in patients with van der Woude and/or popliteal pterygium syndrome, 11 and this has been since reproduced in other studies. 12 Moreover, studies investigating the role of IRF6 in the occurrence of isolated clefts showed strong evidence of overtransmission of the V allele of an intragenic IRF6 polymorphism (V274I) in Asian and South American populations. 13 Moreover, linkage disequilibrium with CL/ P was detected from 40 kbp 5 0 of IRF6 to 135 kbp 3 0 of IRF6 in the Iowan and Danish populations.…”

Section: Introductionmentioning

confidence: 99%

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Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population

et al. 2005

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Cleft lip with or without cleft palate is the most frequent craniofacial malformation in humans (B1/700). Its etiology is multifactorial; some are a result of a genetic mutation, while others may be due to environmental factors, with genetic predisposition playing an important role. The prevalence varies widely between populations and the mode of inheritance remains controversial. The interferon regulatory factor-6 (IRF6) gene has been shown to harbor mutations in patients with van der Woude syndrome, a dominant form of clefts associated with small pits of the lower lip. Moreover IRF6 has been associated with nonsyndromic cleft of the palate (CL/P) in two separate studies. We investigated the role of IRF6 in a set of 195 trios from Belgium. Cleft occurred as an isolated feature. We studied association of the IRF6 locus using two variants: one in the IRF6 gene and the other 100 kpb 3 0 of the gene. Our independent study group confirms that the IRF6 locus is associated with nonsyndromic cleft lip with or without palate. This result, with previous studies performed in the United States and Italy, shows for the first time the implication of IRF6 in isolated CL/P in northern Europe. It is likely that association to this locus can be identified in various populations and that the IRF6 locus thus represents an important genetic modifier for this multifactorial malformation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population

et al. 2005

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“…Interestingly, some of these MCA patients had phenotypes that have been reported in PPS patients (Ghassibe et al. 2004; Sarode et al. 2011].…”

Section: Discussionmentioning

confidence: 99%

The prevalence, penetrance, and expressivity of etiologicIRF6variants in orofacial clefts patients from sub‐Saharan Africa

Gowans

Busch

Mossey

et al. 2017

Molec Gen & Gen Med

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BackgroundOrofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa.MethodsWe carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5′ and 3′ untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants.ResultsWe observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175‐2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants.ConclusionsThis study demonstrates that exons 4 and 7 of IRF6 are mutational ‘hotspots’ in our cohort and that IRF6 mutants‐induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high‐risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms.

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“…The severity of the PPS phenotype could also be partly due to other genetic and environmental factors. Families with individuals with only DVWS and other members with the additional features of PPS have been described [23]. As such, one should consider whether the DVWS and PPS might be interlocked as a single syndrome, connected to the chromosomes 1q32 and 1q34, with variable expressions of features common to both syndromes.…”

Section: Discussionmentioning

confidence: 99%

Interlink of Two Syndromes - Demarquay-van der Woude and Popliteal Pterygium in One Family Group

Htun¹,

Bütow²,

Engelbrecht³

et al. 2016

J Interdiscipl Med Dent Sci

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Six families with van der Woude and/or popliteal pterygium syndrome: all with a mutation in the IRF6 gene

Cited by 54 publications

References 20 publications

Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population

Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population

The prevalence, penetrance, and expressivity of etiologicIRF6variants in orofacial clefts patients from sub‐Saharan Africa

Interlink of Two Syndromes - Demarquay-van der Woude and Popliteal Pterygium in One Family Group

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