A SHMT1 variant decreases the risk of nonsyndromic cleft lip with or without cleft palate in Chile.

SHMT1 变异降低智利非综合征性唇裂伴或不伴腭裂的风险。

  • 影响因子:2.28
  • DOI:10.1111/odi.13229
  • 作者列表:"Salamanca C","González-Hormazábal P","Recabarren AS","Recabarren PA","Pantoja R","Leiva N","Pardo R","Suazo J
  • 发表时间:2020-01-01

OBJECTIVE:To assess the association between polymorphic variants from SHMT1 and MTHFS genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Chilean population. SUBJECTS AND METHODS:In a sample of 139 Chilean NSCL/P cases and 278 controls, we obtained the genotypes for nine variants of SHMT1 and MTHFS and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models. RESULTS:After correction for multiple comparisons, only the variant rs1979277 (G > A; p.Leu474Phe) from SHMT1 showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42-0.86; p = .0054, q = 0.0488) and dominant models (OR 0.48; 95% CI 0.29-0.75; p = .0009; q = 0.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity. CONCLUSIONS:Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and has a higher frequency in controls than in NSCL/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.


目的: 评估参与细胞质无效叶酸周期的SHMT1 和MTHFS基因多态性变异与非综合征性唇裂伴或不伴腭裂 (NSCL/P) 的风险之间的相关性在智利人口中。 受试者和方法: 在 139 例智利NSCL/P病例和 278 例对照的样本中,我们获得了 9 种SHMT1 和MTHFS变异的基因型,并在加性 (等位基因) 、显性和隐性模型中使用比值比 (OR) 评价了它们与表型之间的关联。 结果: 校正多重比较后,仅变异rs1979277 (G > A; p。来自SHMT1 的Leu474Phe) 显示了添加剂的显著和保护作用 (OR 0.60; 95% CI 0.42-0.86; p =。0054,q = 0.0488) 和显性模型 (OR 0.48; 95% CI 0.29-0.75; p =。0009;Q = 0.0081)。我们的生物信息学预测加上以前报告的功能证据证明,这种错义变异的A等位基因会降低酶活性。 结论: 由于rs1979277 A等位基因降低了细胞质SHMT活性,在对照组中的频率高于NSCL/P病例,我们假设低酶活性可能增加叶酸的细胞质浓度,因此,解释了对OFCs的保护作用。



作者列表:["Peyroux E","Babinet MN","Cannarsa C","Madelaine C","Favre E","Demily C","Michael GA"]

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.

作者列表:["Sheridan GA","Nagle M","Howells C","Gallagher O","Kiely PJ","O'Toole P","Kelly PM","Moore DP"]

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.

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作者列表:["Grigoryan G","Korcek L","Eidelman M","Paley D","Nelson S"]

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.

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