Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21.
来自Gabriella Miller Kids First儿科研究联盟的口面裂三联体的全基因组测序确定了 21 号染色体上的一个新位点。
- 作者列表："Mukhopadhyay N","Bishop M","Mortillo M","Chopra P","Hetmanski JB","Taub MA","Moreno LM","Valencia-Ramirez LC","Restrepo C","Wehby GL","Hecht JT","Deleyiannis F","Butali A","Weinberg SM","Beaty TH","Murray JC","Leslie EJ","Feingold E","Marazita ML
:Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic, and the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent-offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case-parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.
: 口面裂隙 (ofc) 是世界上最普遍的颅面出生缺陷之一，并造成了显著的公共卫生负担。大多数OFCs是非综合征型，非综合征型OFCs的遗传病因仅部分确定。在此，我们分析了欧洲和哥伦比亚家系的全基因组序列 (WGS) 数据与OFC风险的相关性，该家系选自一项多中心基于家系的OFC研究。这是第一个大规模的WGS研究OFC在父母-后代三重奏，和加布里埃拉米勒儿童第一个儿科研究计划的一部分，创建儿童癌症和结构性出生缺陷的研究。WGS提供了比在当今单核苷酸多态性 (SNP) 标记面板上使用插补更深入、更具体的遗传数据。使用人类GRCh38 基因组组装，从其序列中调用跨越整个基因组的单核苷酸变异 (SNV) 和短插入和缺失 (indel) 的病例亲本三联体的基因型，并利用传递不平衡检验进行关联分析。在全基因组显著关联中，我们在哥伦比亚家族的 21 号染色体上发现了一个新的位点，以前在拉丁美洲血统的其他更大的OFC样本中没有观察到。该位点位于已知在颅面发育过程中表达的区域内。基于对该位点的更深入调查，我们得出结论，它仅在哥伦比亚人中对OFCs有风险。本研究加强了在OFCs的遗传病因中看到的祖先差异，并强调了在研究OFCs和其他出生缺陷的不同血统人群时需要更大的样本。
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.