A new mutational hotspot in the SKI gene in the context of MFS/TAA molecular diagnosis.


  • 影响因子:4.34
  • DOI:10.1007/s00439-019-02102-9
  • 作者列表:"Arnaud P","Racine C","Hanna N","Thevenon J","Alessandri JL","Bonneau D","Clayton-Smith J","Coubes C","Delobel B","Dupuis-Girod S","Gouya L","Odent S","Carmignac V","Thauvin-Robinet C","Le Goff C","Jondeau G","Boileau C","Faivre L
  • 发表时间:2020-04-01

:SKI pathogenic variations are associated with Shprintzen-Goldberg Syndrome (SGS), a rare systemic connective tissue disorder characterized by craniofacial, skeletal and cardiovascular features. So far, the clinical description, including intellectual disability, has been relatively homogeneous, and the known pathogenic variations were located in two different hotspots of the SKI gene. In the course of diagnosing Marfan syndrome and related disorders, we identified nine sporadic probands (aged 2-47 years) carrying three different likely pathogenic or pathogenic variants in the SKI gene affecting the same amino acid (Thr180). Seven of these molecular events were confirmed de novo. All probands displayed a milder morphological phenotype with a marfanoid habitus that did not initially lead to a clinical diagnosis of SGS. Only three of them had learning disorders, and none had intellectual disability. Six out of nine presented thoracic aortic aneurysm, which led to preventive surgery in the oldest case. This report extends the phenotypic spectrum of variants identified in the SKI gene. We describe a new mutational hotspot associated with a marfanoid syndrome with no intellectual disability. Cardiovascular involvement was confirmed in a significant number of cases, highlighting the importance of accurately diagnosing SGS and ensuring appropriate medical treatment and follow-up.


: SKI致病变异与Shprintzen-Goldberg综合征 (SGS) 相关,SGS是一种罕见的系统性结缔组织疾病,以颅面、骨骼和心血管特征为特征。迄今为止,包括智力障碍在内的临床描述相对同质,已知的致病变异位于SKI基因的两个不同热点。在诊断马凡综合征及相关疾病的过程中,我们确定了 9 例散发先证者 (年龄 2-47 岁) 携带三种不同的可能致病或致病变异的SKI基因,影响相同的氨基酸 (Thr180)。其中 7 个分子事件被重新确认。所有先证者均表现出较温和的形态表型,呈marfanoid习性,最初未导致SGS的临床诊断。其中只有 3 人有学习障碍,没有人有智力障碍。九个中有六个出现胸主动脉瘤,这导致了最古老病例的预防性手术。本报告扩展了SKI基因中鉴定的变异的表型谱。我们描述了一个与无智力障碍的marfanoid综合征相关的新的突变热点。在大量病例中证实了心血管受累,突出了准确诊断SGS和确保适当医疗和随访的重要性。



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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