Vanzo Rena J, Prasad Aparna, Staunch Lauren, Hensel Charles H, Serrano Moises A, Wassman E Robert, Kaplun Alexander, Grandin Temple, Boles Richard G
Lineagen, Inc., Salt Lake City, UT 84109, USA.
Variantyx, Inc., Framingham, MA 01701, USA.
J Pers Med. 2020 Dec 29;11(1):21. doi: 10.3390/jpm11010021.
Autism spectrum disorder (ASD) is a heterogeneous condition with a complex genetic etiology. The objective of this study is to identify the complex genetic factors that underlie the ASD phenotype and other clinical features of Professor Temple Grandin, an animal scientist and woman with high-functioning ASD. Identifying the underlying genetic cause for ASD can impact medical management, personalize services and treatment, and uncover other medical risks that are associated with the genetic diagnosis. Prof. Grandin underwent chromosomal microarray analysis, whole exome sequencing, and whole genome sequencing, as well as a comprehensive clinical and family history intake. The raw data were analyzed in order to identify possible genotype-phenotype correlations. Genetic testing identified variants in three genes (, , and ) that are candidate risk factors for ASD. We identified variants in and , reported to be disease-associated in previous studies, which are likely to contribute to some of her additional clinical features. Moreover, candidate variants in genes encoding metabolic enzymes and transporters were identified, some of which suggest potential therapies. This case report describes the genomic findings in Prof. Grandin and it serves as an example to discuss state-of-the-art clinical diagnostics for individuals with ASD, as well as the medical, logistical, and economic hurdles that are involved in clinical genetic testing for an individual on the autism spectrum.
自闭症谱系障碍（ASD）是一种具有复杂遗传病因的异质性疾病。本研究的目的是确定动物科学家、患有高功能ASD的坦普尔·格兰丁教授的ASD表型及其他临床特征背后的复杂遗传因素。确定ASD的潜在遗传原因可影响医疗管理、使服务和治疗个性化，并揭示与基因诊断相关的其他医疗风险。格兰丁教授接受了染色体微阵列分析、全外显子组测序和全基因组测序，以及全面的临床和家族病史采集。对原始数据进行分析以确定可能的基因型-表型相关性。基因检测确定了三个基因（、和）中的变异，这些变异是ASD的候选风险因素。我们在和中发现了变异，先前研究报道这些变异与疾病相关，它们可能导致了她的一些其他临床特征。此外，还确定了编码代谢酶和转运蛋白的基因中的候选变异，其中一些提示了潜在的治疗方法。本病例报告描述了格兰丁教授的基因组学发现，并作为一个例子来讨论针对ASD个体的最新临床诊断，以及自闭症谱系个体临床基因检测中涉及的医疗、后勤和经济障碍。
