Novel <i>IRF6 </i>mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families

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

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.</p

Maxillomandibular syngnathia in an adult Nigerian patient

Congenital maxillomandibular fusion is a very rare condition with few cases reported worldwide. This paper reports a rare case of bony maxillomandibular fusion of the jaws, with synechiae of buccal mucosa and the gingivae in an adult patient. Separation of the fusion was done under general anesthesia. Isolated cleft of the hard palate was discovered during surgery. This report adds more information to literature, by reporting an adult with syngnathia and isolated cleft of the hard palate

Hemodynamic response after injection of local anesthetics with or without adrenaline in adult Nigerian subjects undergoing simple tooth extraction

Objective: This study was conducted to determine the changes in the blood pressure (BP) and the pulse rate (PR) of normotensive patients having dental extraction under the administration of 2% lignocaine local anesthetic with or without adrenaline. Materials and Methods: This prospective study was carried out on 325 consecutive normotensive patients who presented at the exodontia clinic of the Lagos University Teaching Hospital (LUTH), Lagos, Yoruba State, Nigeria from December 2004 to August 2005 for simple tooth extraction. The patients were randomly allocated into two groups according to the type of anesthetic solution employed. Group A had tooth extraction done under the administration of 2% lignocaine with adrenaline (1:80,000) while group B had tooth extraction done under the administration of 2% lignocaine local anesthetic without vasoconstrictor (plain lignocaine). Each patient had single tooth extracted. The following parameters were monitored in each of the surgical interventions: systolic blood pressure (SBP), diastolic blood pressure (DBP), and PR. Measurements were taken in the waiting room before surgery, during the surgery after local anesthesia, during tooth extraction, and 15 min after tooth extraction. Results: The sample consisted of 176 females and 149 males. Age range of the patients was 18-89 years with the mean age of 35.08 ± 15.60 years. The hemodynamic responses to lignocaine with adrenaline (1:80,000) and plain lignocaine essentially follow the same pattern in the study. There was no statistically significant difference between the measured parameters in the two groups after the administration of local anesthetics. Conclusion: This study, therefore, shows that there was no difference in the hemodynamic changes observed with the use of lignocaine with adrenaline or plain lignocaine during a simple tooth extraction in healthy adults