Novel mutations inIRF6in nonsyndromic cleft lip with or without cleft palate: When shouldIRF6mutational screening be done?

Jehee, Fernanda Sarquis; Burin, Beatriz A.; Rocha, Kátia Maria da; Zechi-Ceide, Roseli Maria; Bueno, Daniela Franco; Brito, Luciano Abreu; Souza, Josiane; Leal, Gabriela Ferraz; Richieri-Costa, Antônio; Alonso, Nivaldo; Otto, Paulo Alberto; Passos‐Bueno, Maria Rita

doi:10.1002/ajmg.a.32849

Cited by 26 publications

(33 citation statements)

References 14 publications

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“…VWS phenocopies non-syndromic cleft lip and palate, as lip pits, the main characteristic feature of VWS, are absent in 15% of the patients. Moreover, polymorphisms in the IRF6 locus are associated with CLP in Caucasians and Asians [Zucchero et al, 2004;Srichomthong et al, 2005;Vieira et al, 2007], and so far, IRF6 mutations were reported in 3/108 NSCL/P families [Jehee et al, 2009]. Interestingly, we identified exonic IRF6 mutations in two a priori diagnosed non-syndromic multiplex CL/P families with an autosomal dominant inheritance and one sporadic case.…”

Section: Discussionmentioning

confidence: 68%

IRF6 Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign

et al. 2010

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Van der Woude syndrome (VWS), caused by dominant IRF6 mutation, is the most common cleft syndrome. In 15% of the patients, lip pits are absent and the phenotype mimics isolated clefts. Therefore, we hypothesized that some of the families classified as having non-syndromic inherited cleft lip and palate could have an IRF6 mutation. We screened in total 170 patients with cleft lip with or without cleft palate (CL/P): 75 were syndromic and 95 were a priori part of multiplex non-syndromic families. A mutation was identified in 62.7 and 3.3% of the patients, respectively. In one of the 95 a priori non-syndromic families with an autosomal dominant inheritance (family B), new insights into the family history revealed the presence, at birth, of lower lip pits in two members and the diagnosis was revised as VWS. A novel lower lip sign was observed in one individual in this family. Interestingly, a similar lower lip sign was also observed in one individual from a 2nd family (family A). This consists of 2 nodules below the lower lip on the external side. In a 3rd multiplex family (family C), a de novo mutation was identified in an a priori non-syndromic CL/P patient. Re-examination after mutation screening revealed the presence of a tiny pit-looking lesion on the inner side of the lower lip leading to a revised diagnosis of VWS. On the basis of this data, we conclude that IRF6 should be screened when any doubt rises about the normality of the lower lip and also if a non-syndromic cleft lip patient (with or without cleft palate) has a family history suggestive of autosomal dominant inheritance.

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Section: Discussionmentioning

confidence: 68%

IRF6 Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign

et al. 2010

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“…Patients with only CP were also excluded, as in most of the cases CP constitutes a different genetic entity from NS CL/P [Fraser, 1974;Jehee et al, 2009]. A final sample of 1,042 families was obtained: 121 from Santar em, 331 from Fortaleza, 86 from Barbalha, 188 from Macei o, and 316 from Rio de Janeiro.…”

Section: Methodsmentioning

confidence: 99%

Genetic contribution for non‐syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies

Brito

Cruz

Rocha

et al. 2011

American J of Med Genetics Pt A

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Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarém, Fortaleza, Barbalha, Maceió, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarém (44%) and the lowest in Maceió (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarém (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceió (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceió to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies.

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“…There are many genes that have been linked with NSCLP like MSX1, TGFB3, TGFA, IRF6, RARA, MTHFR,GABRB3, BCL3,WNT and the list is ever increasing with the latest development in this field. 1,3,4,5,6,7,8 There are various techniques that have been employed in the genetic investigations for NSCLP, the purpose of this review is to present and compare their utility.…”

Section: Introductionmentioning

confidence: 99%

Techniques for Genetic Analysis of Non Syndromal Cleft Lip/Palate: A Review

Singh¹,

Roy²,

Suwal³

et al. 2012

Am. J. Biomed. Sci.

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The formation of craniofacial structures during embryonic development involves various complex molecular pathways. Disturbances in these pathways either due to genetic or environmental factors may lead to orofacial clefts. Approximately two thirds of the cases are not accompanied by other anomalies and are called non syndromic. The etiology seems complex, but genetics plays a major role. With the advances in molecular biology and genetics such studies are more refined than ever before and various candidate genes have been associated with Non Syndromal cleft lip/palate in different populations. There are various techniques and models used by different investigators across the globe. In this review we intend to describe most common approaches towards genetic analysis of Non syndromic cleft and try to evaluate the merits and demerits of a particular approach.

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Novel mutations inIRF6in nonsyndromic cleft lip with or without cleft palate: When shouldIRF6mutational screening be done?

Cited by 26 publications

References 14 publications

<i>IRF6</i> Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign

<i>IRF6</i> Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign

Genetic contribution for non‐syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies

Techniques for Genetic Analysis of Non Syndromal Cleft Lip/Palate: A Review

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