Identification of Developmental and Behavioral Markers Associated With Genetic Abnormalities in Autism Spectrum Disorder.
Identification of Developmental and Behavioral Markers Associated With Genetic Abnormalities in Autism Spectrum Disorder.
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DOI：
10.1176/appi.ajp.2017.16101115
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Thurm A
中科院分区：
文献类型：
--
作者：
Bishop SL;Farmer C;Bal V;Robinson EB;Willsey AJ;Werling DM;Havdahl KA;Sanders SJ;Thurm A
除了一般与神经遗传综合征风险相关的特征（例如，认知障碍），在确定自闭症谱系障碍（ASD）中的表型-基因型关系方面取得的进展有限。本研究通过比较在高置信度ASD相关基因/基因座中具有或不具有鉴定的从头功能丧失突变（LoF）或拷贝数变体（CNV）的ASD先证者的表型谱来扩展Simons Simplex Collection（SSC）中的工作（Sanders等人，2015）。分析先发制人地解释了患有新生突变的受影响个体在性别和智商方面的差异，通过在多个行为领域进行比较之前，将有和没有这些遗传事件的先证者在性别，智商和年龄上进行匹配。具有新生突变的儿童（n=112）在早期发育期间表现出更大的运动延迟可能性（即，但在儿童后期，ASD核心症状的某些指标（父母评定的社交沟通障碍和临床医生评定的诊断确定性）受损较少。这些儿童在言语和语言能力方面也表现出相对优势，包括非言语和言语智商之间的差异较小，并且更有可能达到流利的语言。与那些没有发现遗传异常的ASD儿童相比，具有新生突变的ASD儿童在社交和语言缺陷方面可能表现出“沉默”的症状特征。这些发现表明，检查早期里程碑差异和标准化测试结果可能有助于病因学研究，并可能有助于ASD各种亚型的临床分化，但前提是首先正确考虑发育/人口统计学变量。
Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). This study extends work in the Simons Simplex Collection (SSC) by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations (LoF) or Copy Number Variants (CNV) in high confidence ASD-associated genes/loci (Sanders et al., 2015). Analyses pre-emptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations, by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains. Children with de novo mutations (n=112) showed greater likelihood of motor delays during early development (i.e., later age of walking), but less impairment in certain measures of ASD core symptoms (parent-rated social-communication impairment and clinician-rated diagnostic certainty) in later childhood. These children also showed relative strengths in verbal and language abilities, including a smaller discrepancy between nonverbal and verbal IQ and a greater likelihood of having achieved fluent language. Children with ASD with de novo mutations may exhibit a “muted” symptom profile with respect to social-communication and language deficits, relative to those with ASD with no identified genetic abnormalities. Such findings suggest that examining early milestone differences and standardized testing results may be helpful in etiologic efforts, and potentially in clinical differentiation of various subtypes of ASD, but only if developmental/demographic variables are properly accounted for first.
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影响因子：
3.9
作者：
Gotham, Katherine;Pickles, Andrew;Lord, Catherine
通讯作者：
Lord, Catherine
影响因子：
2
作者：
Morris, Colleen A.;Mervis, Carolyn B.;Paciorkowski, Alex P.;Abdul-Rahman, Omar;Dugan, Sarah L.;Rope, Alan F.;Bader, Patricia;Hendon, Laura G.;Velleman, Shelley L.;Klein-Tasman, Bonita P.;Osborne, Lucy R.
通讯作者：
Osborne, Lucy R.
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
64.8
作者：
Sanders, Stephan J.;Murtha, Michael T.;Gupta, Abha R.;Murdoch, John D.;Raubeson, Melanie J.;Willsey, A. Jeremy;Ercan-Sencicek, A. Gulhan;DiLullo, Nicholas M.;Parikshak, Neelroop N.;Stein, Jason L.;Walker, Michael F.;Ober, Gordon T.;Teran, Nicole A.;Song, Youeun;El-Fishawy, Paul;Murtha, Ryan C.;Choi, Murim;Overton, John D.;Bjornson, Robert D.;Carriero, Nicholas J.;Meyer, Kyle A.;Bilguvar, Kaya;Mane, Shrikant M.;Sestan, Nenad;Lifton, Richard P.;Guenel, Murat;Roeder, Kathryn;Geschwind, Daniel H.;Devlin, Bernie;State, Matthew W.
通讯作者：
State, Matthew W.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y