Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation
Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation
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DOI：
10.1097/00004703-200604002-00012
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发表时间：
2006-04-01
影响因子：
2.4
通讯作者：
Hagerman, Randi
中科院分区：
文献类型：
--
作者：
Farzin, Faraz;Perry, Hazel;Hagerman, Randi
脆性X综合征（FXS）是由FMR 1基因中的完全突变扩增（> 200个CGG重复）引起的，导致脆性X智力低下蛋白缺乏。虽然大多数具有前突变（55-200个CGG重复）的个体被认为不受FXS的影响，但最近的案例研究记录了具有前突变的儿童，他们有认知缺陷，行为问题和/或自闭症谱系障碍。本研究的目的是比较自闭症谱系障碍（ASD）和注意缺陷多动障碍（ADHD）症状的患病率在男孩与前突变谁提出的先证者，在兄弟与前突变谁不提出的先证者，在正常兄弟的前突变和/或全突变携带者。参与者包括43名男性儿童：14名先证者到诊所就诊，13名非先证者通过级联试验（先证者鉴定后对家庭成员进行常规基因检测）确定并确认有前突变，对照组为16名脆性X前突变或完全突变的FMR 1突变阴性的男性兄弟姐妹。参与者来自两个合作地点之一：加州大学戴维斯分校和澳大利亚拉筹伯大学。父母完成了Conners全球指数-父母版本，用于评估ADHD症状和社会沟通问卷（SCQ），用于识别ASD症状。在SCQ上ASD范围内的儿童（n = 13）接受了自闭症诊断观察计划-通用（n = 10）或自闭症诊断访谈-修订版（n = 3）的进一步评估。ASD的最终诊断包括除了标准化评估之外，还使用DSMIV-TR标准进行临床评估。有前突变的男孩作为先证者（p < 0.001）或非先证者（p < 0.001），ASD的发生率较高。
Fragile X syndrome (FXS) is caused by a full mutation expansion (> 200 CGG repeats) in the FMR1 gene that results in a deficiency of the fragile X mental retardation protein. Although most individuals with the premutation (55-200 CGG repeats) are considered unaffected by FXS, recent case studies have documented children with the premutation who have cognitive deficits, behavioral problems, and/or autism spectrum disorders. The objective of this study was to compare the prevalence of autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) symptoms in boys with the premutation who presented as probands, in brothers with the premutation who did not present as probands, and in normal brothers of premutation and/or full mutation carriers. Participants included 43 male children: 14 probands who presented to clinic, 13 nonprobands who were identified through cascade testing (routine genetic testing of family members after identification of a proband) and confirmed to have the premutation, and a control group of 16 male siblings of individuals with the fragile X premutation or full mutation who were negative for the FMR1 mutation. Participants came from 1 of 2 collaborative sites: University of California, Davis and La Trobe University in Australia. Parents completed the Conners' Global Index-Parent Version for assessing symptoms of ADHD and the Social Communication Questionnaire (SCQ) for identifying symptoms of ASD. Children who were in the ASD range on the SCQ (n = 13) underwent further evaluation with either the Autism Diagnostic Observation Schedule-Generic (n = 10) or the Autism Diagnostic Interview-Revised (n = 3). A final diagnosis of ASD included clinical assessment utilizing DSMIV-TR criteria in addition to the standardized assessments. There was a higher rate of ASD in boys with the premutation presenting as probands (p < 0.001) or nonprobands (p