Research progress on the role of environmentally induced DNA methylation in congenital cleft lip and/or palate / 口腔疾病防治

@#Congenital cleft lip and/or palate (CL/P) is a common malformation of maxillofacial development. At present, it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmental factors. Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congenital malformations. As one of the important epigenetic modifications, DNA methylation has been widely and deeply studied in many fields, but as a link between the individual and the environment, its application in CL/P is limited. Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate. Stimulation of folate deficiency, smoking, pollutant exposure and other environmental factors can induce changes in the state of DNA methylation, thus affecting gene expression in the development of lip and palate and leading to the occurrence of deformities.

Clinical and genetic features of Chinese kindreds with Van der Woude syndrome caused by interferon regulatory factor 6 mutation / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the clinical phenotype and genetic characteristics of Chinese families with Van der Woude syndrome (VWS).@*METHODS@#Clinical manifestations between 14 families and within each family were recorded. Possible inheritance modes and pathogenic genes were analyzed. Phenotypic distribution and gene frequencies were calculated.@*RESULTS@#Of the pedigrees investigated, an autosomal dominant inheritance pattern was suggested. All patients had typical symptoms. The pathogenic gene was interferon regulatory factor 6 (IRF6). Phenotypic distribution frequencies were as follows: lip pits (91.9%), cleft lip and/or palate (73.0%), and hyperdontia (8.1%). There were significant differences in clinical phenotypes among individuals of different families and individuals of the same family.@*CONCLUSIONS@#VWS in a Chinese population was dominantly inherited with high penetrance and variable expressivity. The pathogenic gene was IRF6. VWS in a Chinese population was genotyped as VWS1.

Cleft lip and cleft palate in Jangxi province: A case-control study on familial occurrence of 1 967 cases / 实用口腔医学杂志

Objective:To assess whether familial occurrence has an influence on the morphological characteristics of patients with nonsyndromic cleft lip and/or palate (NsCL/P).Methods:A case-control analysis was performed on the morphological characteristics of familial group and sporadic group,using medical records of 1967 patients with NsCL/P treated in the Affiliated Stomatological Hospital of Nanchang University from 2002 to 2014.Results:164 (8.34％) cases presented a positive history of cleft in their families.The cleft types,the positive familial rate of cleft lip only (CLO),cleft lip and alveolar ridge(CLA),cleft lip and palate (CLP) and cleft palate only (CPO) were 8.11％,8.54％,6.19％ and 9.65％ respectively.A positive family history of NsCL/P was associated with 0.66 times risk of CPO (P =0.036,OR =0.66,95％ CI 0.44-0.98) compared to those of CLO,CLA and CLP.In familial group of CLP,the lateral incidence of male patients was different from that of female patients (P ＜ 0.001).There was no significant difference between familial group and sporadic group on birth weights,parental child-bearing age and clinical manifestations of patients.Conclusion:Familial occurrence might have an influence on cleft type,laterality and gender of the patients with NSCL/P.

Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Nonsyndromic Cleft Lip and/or Palate

The aim of this study was to evaluate the association of the polymorphisms in TCN2 (rs1801198) gene and in MTRR (rs1801394) gene with nonsyndromic cleft lip and/or palate (NSCL/P) in a Brazilian population. Genomic DNA was extracted from buccal cells. The polymorphisms in TCN2 (rs1801198) and MTRR (rs1801394) genes were genotyped by carrying out real-time PCR and Taqman assay. Chi-square test was used to determine the association between genotype and allele frequencies with NSCL/P and NSCL/P subgroups (cleft lip only, cleft lip and palate, and cleft palate only). Eight hundred and sixty seven unrelated individuals (401 cases with NSCL/P and 466 individuals without cleft) were evaluated. Genotype distributions of TCN2 and MTRR polymorphisms were in Hardy-Weinberg equilibrium. The TCN2 polymorphic genotype GG was identified in 16.7% of the NSCL/P group and in 14.1% of the non-cleft group (p>0.05). Similarly, the frequency of MTRR genotype (GG) was similar in NSCL/P group (15.5%) and control group (17.8%) (p>0.05). Multivariate analysis showed an association between MTRR and the subgroup that the mother smoked during pregnancy (p=0.039). Our findings did not demonstrate an association between TCN2 polymorphisms and NSCL/P, however suggests an association between MTRR and NSCL/P etiology.

Resumo O objetivo desse estudo foi avaliar a associação entre os polimorfismos no gene TCN2 (rs1801198) e no gene MTRR (rs1801394) com fissura de lábio e/ou palato não sindrômica (NSFL/P) em uma população brasileira. DNA genômico foi extraído de células bucais. Os polimorfismos nos genes TCN2 (rs1801198) e MTRR (rs1801394) foram genotipados através do PCR em tempo real pelo método Taqman. O teste do qui-quadrado foi utilizado para determinar a associação entre a frequência alélica e genotípica e NSFL/P e nos subtipos (fissura de lábio, fissura de lábio com palato e fissura de palato). Oitocentos e sessenta e sete indivíduos não aparentados (401 casos com NSFL/P e 466 indivíduos sem fissura) foram avaliados. A distribuição dos genótipos dos polimorfismos de TCN2 e MTRR estavam em equilíbrio de Hardy-Weinberg. O genótipo polimórfico GG do gene TCN2 foi identificado em 16,7% do grupo com NSFL/P e em 14,1% do grupo sem fissura (p>0,05). Da mesma forma, a freqüência do genótipo GG do gene MTRR foi bastante semelhante entre o grupo com NSFL/P (15,5%) e o grupo controle (17,8%). A análise multivariada mostrou associação entre o gene MTRR e o subgrupo que apresentou tabagismo materno durante a gestação (p=0,039). Nossos resultados mostraram que não há associação entre os polimorfismos nos genes TCN2 e NSFL/P, entretanto sugerem uma associação entre MTRR e a etiologia de NSFL/P.

Prenatal Diagnosis of Accompanying Alveolar Cleft and Cleft Palate in Fetuses with Cleft Lip Using Prenatal 3D Sonographic Identification and Antenatal Counseling

PURPOSE: Cleft lip and/or palate is the most common congenital facial anomaly whose incidence is about 1 in 500~1000 live births. As this anomaly may be associated with the serious chromosomal anomalies or the multiple organ abnormalities resulting in the fetal loss or perinatal maternal morbidity and mortality, careful prenatal counseling with early and accurate detection is important. Although conventional prenatal ultrasound(US) examination in midterm pregnancy has been applied for screening of cleft lip, there are definite limitations in the diagnosis of accompanying cleft palate or alveolar cleft. We applied high-resolution 3D US along the serial axial, coronal and sagittal plane so that we could diagnose the cleft palate and/or alveolar cleft in fetuses with cleft lip. METHODS: From May 2005 to September 2005, 20 fetuses with cleft lip were examined with prenatal 3D US. Average maternal age was 28.8 years old(24-35 years old), and average gestational age was 24.8 weeks(17.6 to 34.2 weeks). Consecutive axial, coronal and sagittal multislice view were obtained via prenatal 3D US examination and diagnosis of cleft palate and/or alveolar cleft in cleft lip fetuses was followed. RESULTS: With noninvasive and safe prenatal 3D US examination, 17 of 20 cleft lip fetuses were demonstrated to have cleft palate and/or alveolar cleft. Prenatal counseling according to the result was made. CONCLUSION: Existing prenatal US examination is suitable for screening the cleft lip fetuses but has limitation in identifying the related existence of cleft palate and/ or alveolar cleft. Authors verify the presence of cleft palate and/or alveolar cleft acquiring the successive multislice axial, coronal, and sagittal view with prenatal 3D US examination. Therefore, prenatal 3D US examination could be regarded as a noninvasive and secure screening modality in fetuses with cleft lip for confirming whether cleft palate and/or alveolar cleft is accompanied.

Clinical study on the anomalies of number and morphology in cleft lip and palate patients' teeth / 대한치과교정학회지

Cleft lip and/or palate (CLP) is one of the most common congenital craniofacial anomalies and occurs more frequently in Asian people. Dental abnormalities in number, size, shape, and eruption of teeth are frequently associated with CLP. The purposes of this study were to investigate the effects of CLP on number, size, shape and eruption of teeth and to provide basic clinical data for diagnosis and treatment of the CLP patients. With the orthodontic and cleft charts, diagnostic models, orthopantomograms and intraoral x-ray films from 241 CLP patients who visited Dept. of Orthodontics, Seoul National University Dental Hospital, we evaluated the frequency of congenital missing teeth, supernumerary teeth, impacted teeth, and microdontia. The results were as follows ; 1. Frequency of congenital missing was relatively high up to 56.8 %. Congenital missing occurred frequently in the maxillary lateral incisor and the maxillary second premolar. Among the CLP types, frequencies of congenital missing in cleft lip and palate group and cleft lip and alveolus group were higher than those of cleft lip group and cleft palate group. And bilateral cleft showed higher frequencies than unilateral ones. 2. Supernumerary tooth was shown in 11.2 % of CLP patients. It occurred frequently in the area between the maxillary lateral incisors and the maxillary canine. Among the CLP types, cleft lip group showed relatively most highest frequency. 3. Impaction was shown in 18.3 % of CLP patients. It occurred most frequently in the maxillary lateral incisor and the maxillary canine than other teeth. Among the CLP types, cleft lip group and cleft lip and palate group showed most highest frequencies. 4. Microdontia was shown in 15.8 % of CLP patients. It occurred the most frequently in the maxillary lateral incisors and maxillary canines. Among the CLP types, cleft lip and alveolus group and cleft lip and palate group showed relatively higher frequencies. There was no microdontia in cleft palate group.

The study on the cleft lip and/or palate patients who visited Dept. of The study on the cleft lip and/or plate patients who visited Dept. of Orthodontics, Seoul National University Dental Hospital during last11 years(198 / 대한치과교정학회지

Cleft lip and/or palate is one of the most common congenital craniofacial anomalies. According to previous epidemiologic studies, incidence of cleft lip and/or palate has been increasing nowadays. However, there is no report about epidemiologic study of cleft lip and/or palate patients who visited dept. of orthodontics in Korea. So the purpose of this study was to provide the epidemiological characteristics and important basic clinical data for the diagnosis and the treatment of the cleft lip and/or palate patients. With the orthodontic and the charts, diagnostic models and X-ray films from 250 patients with cleft lip and/or palate who visited Dept. of Orthodontics, Seoul National University Dental Hospital during the last 11 years, the authors investigated patient`s visiting year, types of cleft, patient`s gender, and Angle`s classification of malocclusion, and surgery timing. 1. The number of cleft patients who visited Dept. of Orthodontics, SNUDH increased during 1988-1990and then it declined until 1992. From 1993 to 1996, it showed a stationary trend. After 1997 it showed an overwhelmingly increasing trend. 2. In the cleft type, the ratio of cleft lip : cleft lip and alveolus : cleft palate : cleft lip and palate was 7.6 : 19.2 : 9.6 : 63.6. In cleft position, unilateral clefts were more than bilateral ones (cleft lip 79 : 21, cleft lip and alveolus 77 : 23, cleft lip and palate 75.5:24.5). In cleft side, left clefts were more than right cleft (cleft lip 53.3 : 46.7, cleft lip and alveolus 59.5 : 40.5, cleft lip and palate 59.2 : 40.8). 3. In gender ratio, males were more than females in cleft lip (57.9 : 42.1), cleft lip and alveolus (68.8 : 31.2) and cleft lip and palate (76.1 : 23.9). But in cleft palate females were more than males as 41.7 : 58.3. 4. In the age groups, 7-12 year group was the most abundant as 52%, and then 0-6 year group (20.4%), 13-18 year group (17.2%), more than 18 year group (10.4%) were followed as descending order. 5. Most of the cleft lip repair surgeries were operated in 0-3 month (60.3%) and 4-6 month (17.9%). 6. The cleft palate repair surgeries were done in 1-2 year (31.7%), 0-1 year (25.6%), 2-3 year (12.1%), more than 5 year (11.6%) as descending order. 7. The lip scar revision surgeries were done before admission at elementary school 60%. (4-6 year (27.5%), 6-8 year (19.6%), more than 10 year (19.6%), 2-4 year (13.7%) as descending order) 8. The rhinoplasties were done before admission at elementary school in 51.7%. (0-2 year (7.1%), 2-4 year (14.3%), 4-6 year (21.4%), 6-8 year (14.3%)) 9. The pharyngeal flap were done at 6 Y (72.5 months) after birth on average and there was even distribution of surgery timing. 10. In relationship between Angle`s classification of malocclusion and cleft types, Class I was most abundant and Class III, Class II were followed as descending order in cleft lip group. But Class III was most abundant and Class I, Class II were followed as descending order in cleft lip and alveolus group, cleft plate group, and cleft lip and palate group. The percentage of frequency in Class III malocclusion was overwhelmingly higher in cleft lip and palate group than any other groups. 11. Because the frequency of Class III malocclusion was most prevalent in all age groups, anterior crossbite was the most common chief complaint of cleft patients.