Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population.
- 作者列表："Azevedo CMS","Machado RA","Martelli-Júnior H","Reis SRA","Persuhn DC","Coletta RD","Rangel ALCA
OBJECTIVE:To investigate the association of single-nucleotide polymorphisms (SNP) in grainyhead-like 3 (GRHL3) and to verify its possible interactions with others genes responsible for craniofacial development in the risk of non-syndromic oral cleft (NSOC). METHODS:Applying TaqMan allelic discrimination assays, we evaluated GRHL3 SNPs (rs10903078, rs41268753, and rs4648975) in an ancestry-structured case-control sample composed of 1,127 Brazilian participants [272 non-syndromic cleft palate only (NSCPO), 242 non-syndromic cleft lip only (NSCLO), 319 non-syndromic cleft lip and palate (NSCLP), and 294 healthy controls]. Additionally, SNP-SNP interactions of GRHL3 and previously reported variants in FAM49A, FOXE1, NTN1, and VAX1 were verified in non-syndromic cleft lip with or without cleft palate (NSCL ± P). To eliminate false-positive associations, Bonferroni correction or 1,000 permutation method was applied. RESULTS:The multiple logistic regression analysis showed that the CC genotype of rs10903078 (p = .03) and the haplotype C-C formed by the SNPs rs10903078 and rs41268753 (p = .04) were associated with NSCLO, but the p-values did not withstand Bonferroni correction. However, SNP-SNP test revealed significant interactions between GRHL3 SNPs and FAM49A (rs7552), FOXE1 (rs3758249), VAX1 (rs7078160 and rs751231), and NTN1 (rs9891446). CONCLUSIONS:Our results confirm the importance of GRHL3 and its interactions with previously NSOC-associated genes, including FAM49A, FOXE1, NTN1, and VAX1, in the pathogenesis of NSOC in the Brazilian population.
目的: 探讨grainyhead-like 3 (GRHL3) 基因单核苷酸多态性 (SNP) 的相关性。并验证其与非综合征性口腔裂 (NSOC) 风险中与其他负责颅面发育的基因可能的相互作用。 方法: 应用TaqMan等位基因辨别试验，我们评价了GRHL3 SNPs (rs10903078 、rs41268753 和rs4648975) 在由 1,127 名巴西参与者组成的祖先结构的病例对照样本中 [272 只非综合征性腭裂 (NSCPO)，242 只非综合征性唇裂 (NSCLO)，319 例非综合征性唇腭裂 (NSCLP)，294 例健康对照]。此外，在非综合征性唇裂伴或不伴腭裂中验证了GRHL3 的SNP-SNP相互作用和以前报道的FAM49A、FOXE1 、NTN1 和VAX1 的变异 (NSCL ± P)。为了消除假阳性关联，采用Bonferroni校正或 1,000 排列法。 结果: 多元logistic回归分析显示，rs10903078 的CC基因型 (p = .03) 和SNPs rs10903078 和rs41268753 形成的单倍型C-C (p = .04) 与NSCLO相关，但p值不耐受Bonferroni校正。然而，SNP-SNP检测发现GRHL3 SNPs与FAM49A (rs7552) 、FOXE1 (rs3758249) 、VAX1 (rs7078160 和rs751231) 和NTN1 (rs9891446) 之间存在显著的相互作用。 结论: 我们的结果证实了GRHL3 及其与先前NSOC相关基因，包括FAM49A、FOXE1 、NTN1 和VAX1 在巴西人群NSOC发病中的重要性及其相互作用。
METHODS::Impairments in social cognition have been frequently described in 22q11.2 deletion syndrome (22q11.2DS) and are thought to be a hallmark of difficulties in social interactions. The present study addresses aspects that are critical for everyday social cognitive functioning but have received little attention so far. Sixteen children with 22q11.2DS and 22 controls completed 1 task of facial expression recognition, 1 task of attribution of facial expressions to faceless characters involved in visually presented social interactions, and 1 task of attribution of facial expressions to characters involved in aurally presented dialogues. All three tasks have in common to involve processing of emotions. All participants also completed two tasks of attention and two tasks of visual spatial perception, and their parents completed some scales regarding behavioural problems of their children. Patients performed worse than controls in all three tasks of emotion processing, and even worse in the second and third tasks. However, they performed above chance level in all three tasks, and the results were independent of IQ, age and gender. The analysis of error patterns suggests that patients tend to coarsely categorize situations as either attractive or repulsive and also that they have difficulties in differentiating emotions that are associated with threats. An isolated association between the tasks of emotion and behaviour was found, showing that the more frequently patients with 22q11.2DS perceive happiness where there is not, the less they exhibit aggressive behaviour.
METHODS:BACKGROUND:We describe the first radiographic clinic in the literature for DDH and how this novel clinic can significantly improve the efficiency and cost-effectiveness of service in a tertiary referral centre. AIMS:A radiographic clinic for the management of developmental dysplasia of the hip was introduced in 2017 in our institution. We performed a detailed cost analysis to assess the economic savings made with the introduction of this new clinic. We assessed the efficiency of the service by identifying how many unnecessary outpatient visits were prevented. We also assessed the difference in times from referral to review between the two clinics. METHODS:Analysis of the clinic activity in 2017 was possible as all data was collected prospectively by the DDH CNS and stored in our database. Cost analysis was performed, and the savings made per patient along with the financial benefit to our institution was recorded. RESULTS:The new radiographic clinic reduced the cost of reviewing one patient by €162.51 per patient. There was a 73% discharge rate from the clinic which prevented 251 unnecessary patient visits to the outpatient department over the course of the year. There was a significant 11-day reduction in waiting times between referral and review when comparing the radiographic to the conventional clinic (p < 0.05). CONCLUSIONS:A radiographic clinic for the management of developmental dysplasia of the hip has a significant effect on the efficiency and overall cost-effectiveness of service provision in a tertiary referral centre.
METHODS:INTRODUCTION:Triple pelvic osteotomy (TPO) involves periacetabular osteotomies of the ilium, ischium, and pubis to reorient the acetabulum. This operation is indicated in certain situations for the treatment of developmental dysplasia of the hip, dysplastic neuromuscular hips, and for containment of the femoral head in cases of Legg-Calvé-Perthes disease. METHODS:This retrospective cohort study compares radiographic outcomes of patients who underwent TPO using two different techniques and describes a novel single-incision direct lateral approach. TPO was performed on 22 patients by the senior author. The first 10 patients underwent TPO through a single-incision anterolateral approach. The last 12 patients underwent TPO using the direct lateral approach. Preoperative and postoperative pelvic radiographs were reviewed for each patient, and the migration index and center-edge angle were recorded. RESULTS:The migration index and center-edge angle were evaluated and were not found to be significantly different between the anterolateral and direct lateral groups. The direct lateral approach is described. CONCLUSION:The direct lateral approach for TPO is equivalent to the anterolateral approach on radiographic evaluation. Advantages of the direct lateral approach include direct visualization of the ischial osteotomy, effective mobilization of the acetabulum, and safety of the sciatic nerve.