Autism Spectrum Disorder Symptom Profile Across the RASopathies.
Autism Spectrum Disorder Symptom Profile Across the RASopathies.
复制标题
DOI：
10.3389/fpsyt.2020.585700
复制
发表时间：
2020
影响因子：
4.7
通讯作者：
Garg S
中科院分区：
文献类型：
--
作者：
Geoffray MM;Falissard B;Green J;Kerr B;Evans DG;Huson S;Burkitt-Wright E;Garg S
Ras MAPK信号通路的失调与自闭症谱系障碍（ASD）的发病机制有关。RASopathies是一组由Ras/MAPK途径基因突变引起的疾病，具有许多重叠的临床特征。研究表明ASD在RASopathies中的患病率很高，但缺乏ASD特征的详细描述。本研究的目的是比较与功能获得性和功能丧失性突变相关的三种不同RASopathy的ASD症状特征：1型神经纤维瘤病（NF 1），努南综合征（NS）和心面皮肤综合征（CFC）。参与者从现有的数据库中抽取，如果他们被诊断为RASopathy，符合ASD的标准，并且能够口头交流。我们在自闭症诊断量表（ADI-R）和自闭症诊断观察表（ADOS）上比较了NF 1 + ASD（n = 48）、NS + ASD（n = 11）和CFC + ASD（n = 7）的表型特征。我们发现，与NS和CFC组相比，NF 1组的社会障碍水平较高，限制性重复行为较低，存在细微但不显著的组间差异。我们观察到发育里程碑的组间差异，CFC最严重的延迟，其次是NS和NF 1。我们的研究结果表明，尽管发育差异，ASD配置文件仍然相对一致的三个RASopathies。虽然我们的结果需要在更大的样本中确认，但它们表明，在一种RAS病的背景下开发的治疗和机制见解可能适用于其他人，并可能适用于与Ras/MAPK通路基因失调相关的非综合征型ASD。
Dysregulation of the Ras MAPK signaling pathway is implicated in the pathogenesis of autism spectrum disorder (ASD). The RASopathies, a group of disorders caused by mutations of the Ras/MAPK pathway genes, share many overlapping clinical features. Studies suggest a high prevalence of ASD in the RASopathies, but detailed characterization of the ASD profile is lacking. The aim of this study was to compare the ASD symptom profile of three distinct RASopathies associated with both gain-of-function and loss-of-function mutations: neurofibromatosis type 1 (NF1), Noonan syndrome (NS), and cardiofaciocutaneous syndrome (CFC). Participants were drawn from existing databases if they had a diagnosis of a RASopathy, met the criteria for ASD, and were able to communicate verbally. We compared the phenotypic profile of NF1 + ASD (n = 48), NS + ASD (n = 11), and CFC + ASD (n = 7) on the Autism Diagnostic Inventory (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). We found subtle but non-significant group differences with higher levels of social impairments and lower restricted repetitive behaviors in the NF1 group as compared with the NS and CFC groups. We observed group differences in developmental milestones with most severe delays in CFC, followed by NS and NF1. Our results suggest that despite developmental differences, the ASD profile remains relatively consistent across the three RASopathies. Though our results need confirmation in larger samples, they suggest the possibility that treatment and mechanistic insights developed in the context of one RASopathy may be generalizable to others and possibly to non-syndromic ASD associated with dysregulation of Ras/MAPK pathway genes.
登录
查看更多内容
影响因子：
3.8
作者：
Garg, Shruti;Brooks, Ami;Green, Jonathan
通讯作者：
Green, Jonathan
影响因子：
3.7
作者：
Bruining H;de Sonneville L;Swaab H;de Jonge M;Kas M;van Engeland H;Vorstman J
通讯作者：
Vorstman J
影响因子：
7
作者：
Curran, Patrick J.;Hussong, Andrea M.
通讯作者：
Hussong, Andrea M.
影响因子：
25
作者：
Gazestani, Vahid H.;Pramparo, Tiziano;Lewis, Nathan E.
通讯作者：
Lewis, Nathan E.
影响因子：
3.9
作者：
Hus, Vanessa;Lord, Catherine
通讯作者：
Lord, Catherine