Microdeletion of the entire IRF6 gene in a Subsaharian African’s family with Van der Woude syndrome

Mbuyi-Musanzayi, Sébastien; Kasamba, Eric; Revençu, Nicole; Lukusa, Prosper Tshilobo; Kalenga, Prosper Muenze Kayamba; Tshilombo, François Katombe; Reychler, Hervé; Devriendt, Koenraad

doi:10.1097/mcd.0000000000000272

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…Therefore, we hypothesized that the genes controlling tooth formation are closely related to those contributing to the cleft formation. Previously, a significant association between markers in interferon regulatory factor 6 (IRF6), Wnt family member 3 A (WNT3A), and bone morphogenetic protein 5 (BMP5) genes among orofacial cleft and tooth agenesis was found; however, variants of Fas-associated factor 1 (FAF1) and grainyhead-like transcription factor 3 (GRHL3) genes contributed only to craniofacial development [ 9 – 12 ]. The IRF6 gene encodes a transcription factor that contributes to the formation of the oral ectoderm, periderm, and lip as well as the regulation of palatal shelf migration, adhesion, and fusion [ 13 ].…”

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confidence: 99%

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Ghazali,

Rahman,

Kannan

et al. 2023

BMC Oral Health

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Background Nonsyndromic cleft lip and/or without cleft palate (NSCL/P) with or without hypodontia is a common developmental aberration in humans and animals. This study aimed to identify the loss of heterozygosity (LOH) involved in hypodontia and NSCL/P pathogenesis. Methods This is a cross-sectional study that conducted genome-wide copy number analysis using CytoScan 750K array on salivary samples from Malay subjects with NSCL/P with or without hypodontia aged 7–13 years. To confirm the significant results, simple logistic regression was employed to conduct statistical data analysis using SPSS software. Results The results indicated the most common recurrent copy neutral LOH (cnLOH) observed at 1p33-1p32.3, 1q32.2-1q42.13 and 6p12.1-6p11.1 loci in 8 (13%), 4 (7%), and 3 (5%) of the NSCL/P subjects, respectively. The cnLOHs at 1p33-1p32.3 (D1S197), 1q32.2-1q42.13 (D1S160), and 6p12.1-6p11.1 (D1S1661) were identified observed in NSCL/P and noncleft children using microsatellite analysis markers as a validation analysis. The regions affected by the cnLOHs at 1p33-1p32.3, 1q32.2-1q42.13, and 6p12.1-6p11.1 loci contained selected genes, namely FAF1, WNT3A and BMP5, respectively. There was a significant association between the D1S197 (1p33-32.3) markers containing the FAF1 gene among NSCL/P subjects with or without hypodontia compared with the noncleft subjects (p-value = 0.023). Conclusion The results supported the finding that the genetic aberration on 1p33-32.3 significantly contributed to the development of NSCL/P with or without hypodontia. These results have an exciting prospect in the promising field of individualized preventive oral health care.

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Section: Introductionmentioning

confidence: 99%

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Ghazali,

Rahman,

Kannan

et al. 2023

BMC Oral Health

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Non‐random distribution of deleterious mutations in the DNA and protein‐binding domains of IRF6 are associated with Van Der Woude syndrome

Alade

Buxó-Martínez

Mossey

et al. 2020

Molec Gen & Gen Med

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Background The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well‐organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA‐binding (exon 3, 4) or protein‐binding domains (exon 7–9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico. Methods We used PubMed with the search terms; "Van der Woude syndrome," “Popliteal pterygium syndrome,” "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants. Results Twenty‐one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7–9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein‐binding domain (exon 7–9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*). Conclusion Mutations in the protein and DNA‐binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.

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Microdeletion of the entire IRF6 gene in a Subsaharian African’s family with Van der Woude syndrome

Cited by 2 publications

References 24 publications

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Non‐random distribution of deleterious mutations in the DNA and protein‐binding domains of IRF6 are associated with Van Der Woude syndrome

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