Prospective and detailed behavioral phenotyping in DDX3X syndrome.
Prospective and detailed behavioral phenotyping in DDX3X syndrome.
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DOI：
10.1186/s13229-021-00431-z
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发表时间：
2021-05-16
期刊：
影响因子：
6.2
通讯作者：
Grice DE
中科院分区：
文献类型：
--
作者：
Tang L;Levy T;Guillory S;Halpern D;Zweifach J;Giserman-Kiss I;Foss-Feig JH;Frank Y;Lozano R;Belani P;Layton C;Lerman B;Frowner E;Breen MS;De Rubeis S;Kostic A;Kolevzon A;Buxbaum JD;Siper PM;Grice DE
DDX3X综合征是最近发现的一种遗传性疾病，占女性不明原因发育迟缓和/或智力残疾（ID）病例的1-3%，并与运动和语言迟缓以及自闭症谱系障碍（ASD）有关。迄今为止，已发表的该综合征的表型特征主要依赖于病历审查；此外，该综合征的行为维度尚未得到充分探讨。我们对14名女性和1名男性的DDX3X综合征进行了多日、前瞻性、详细的表型分析，重点关注行为、心理和神经学方面的测量。该队列中的三名参与者先前报告的表型信息有限，并为本研究重新评估。我们将结果与群体标准进行比较，并对比了携带(1)蛋白质截断变异或(2)错义变异或框架内缺失的个体之间的表型。80%的人符合ID的标准，60%符合ASD的标准，53%符合注意缺陷/多动障碍（ADHD）的标准。运动和语言迟缓很常见，感觉处理异常也很常见。该队列包括5个错义，3个内含子/剪接位点，2个无义，2个移码，2个帧内缺失和1个起始密码子变异。基因型-表型相关性表明，平均而言，与蛋白质截断变异相比，错义变异/帧内缺失与更严重的语言、运动和适应性缺陷相关。然而，样本量适中，DDX3X综合征是一种罕见且未被诊断的疾病。这项研究首次对DDX3X综合征进行了前瞻性的详细描述，扩展了我们对神经行为表型的理解。金标准诊断方法显示了高的ID， ASD和ADHD的发生率。此外，感觉缺陷被认为是该综合征的关键部分。即使是适度的样本，我们也观察到基因型-表型相关性与错义变异/框内缺失通常与更严重的表型相关的证据。在线版本包含补充材料，可在10.1186/s13229-021-00431-z获得。
DDX3X syndrome is a recently identified genetic disorder that accounts for 1–3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype–phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants. Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder. This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype–phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes. The online version contains supplementary material available at 10.1186/s13229-021-00431-z.
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作者：
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影响因子：
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DOI：
10.1073/pnas.1806811115
发表时间：
2018-12-18
影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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