Arutiunian Vardan, Santhosh Megha, Neuhaus Emily, Sullivan Catherine A W, Bernier Raphael A, Bookheimer Susan Y, Dapretto Mirella, Geschwind Daniel H, Jack Allison, McPartland James C, Van Horn John D, Pelphrey Kevin A, Gupta Abha R, Webb Sara Jane
Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, Washington, USA.
Department of Psychiatry and Behavioral Science, University of Washington, Seattle, Washington, USA.
Autism Res. 2024 Jul 10. doi: 10.1002/aur.3193.
One of the candidate genes related to language variability in individuals with Autism Spectrum Disorder (ASD) is the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family. However, due to the different assessment tools used, it is unknown whether the polymorphisms of the CNTNAP2 gene are linked to structural language skills or more general communication abilities. A total of 302 youth aged 7 to 18 years participated in the present study: 131 verbal youth with ASD (62 female), 130 typically developing (TD) youth (64 female), and 41 unaffected siblings (US) of youth with ASD (25 female). Blood samples were collected to obtain genomic DNA and processed by the Rutgers University Cell and Data Repository or using standard protocols (Gentra Puregene Blood DNA extraction kit; Qiagen). Language and verbal communication skills were screened with the Clinical Evaluation of Language Fundamental-4 (CELF-4) and Vineland-II Communication domain, subsequently. The results showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. No relationship was found between the polymorphism of CNTNAP2 and more general communication abilities. Although the study revealed genetic mechanisms that are associated with CELF-4 measures but not Vineland-II in youth with ASD, follow-up studies are needed that will include measures of language and communication that are less correlated to each other as well as will include a group of minimally and/or non-verbal individuals with ASD.
与自闭症谱系障碍(ASD)个体语言变异性相关的候选基因之一是接触蛋白相关蛋白样2基因(CNTNAP2),它是神经纤连蛋白家族的一员。然而,由于所使用的评估工具不同,尚不清楚CNTNAP2基因的多态性是否与结构性语言技能或更一般的沟通能力相关。共有302名7至18岁的青少年参与了本研究:131名患有ASD的语言能力正常的青少年(62名女性),130名发育正常(TD)的青少年(64名女性),以及41名ASD青少年的未受影响的兄弟姐妹(US)(25名女性)。采集血样以获取基因组DNA,并由罗格斯大学细胞与数据储存库进行处理或使用标准方案(Gentra Puregene血液DNA提取试剂盒;Qiagen)。随后,使用语言基本能力临床评估量表-4(CELF-4)和文兰适应行为量表第二版沟通领域对语言和言语沟通技能进行筛查。结果表明,CNTNAP2的多态性(SNP rs2710102)与结构性语言能力相关,携带A等位基因的参与者与G等位基因纯合子相比语言技能较低。未发现CNTNAP2的多态性与更一般的沟通能力之间存在关联。尽管该研究揭示了与ASD青少年中CELF-4测量相关但与文兰适应行为量表第二版无关的遗传机制,但仍需要进行后续研究,包括使用相互关联较小的语言和沟通测量方法,以及纳入一组轻度和/或无语言能力的ASD个体。