Hnoonual Areerat, Kor-Anantakul Phawin, Charalsawadi Chariyawan, Worachotekamjorn Juthamas, Limprasert Pornprot
Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Front Genet. 2021 Sep 22;12:755605. doi: 10.3389/fgene.2021.755605. eCollection 2021.
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which are etiologically heterogeneous. Chromosomal microarray is now recommended as the first-tier clinical diagnostic test for ASD. We performed chromosomal microarray in 16 Thai patients with ASD using an Illumina HumanCytoSNP-12 v2.1 array and found one case with uniparental disomy (UPD) of chromosome 15. Methylation-specific PCR showed abnormal methylation of the maternal allele. Haplotype analysis revealed that the patient had received both chromosomes 15 from his father. These results were consistent with Angelman syndrome. However, his clinical features had no clinical significance for classic Angelman syndrome. He had first presented at the pediatric clinic with no speech, poor social interaction skills and repetitive behaviors consistent with ASD based on the DSM-IV criteria at 2 years of age and later confirmed by ADOS at 5 years of age. He was strikingly overweight but had no dysmorphic facies, seizures nor ataxia and was diagnosed as non-syndromic ASD, a diagnosis which was believed until at 10 years of age, his DNA was included for analysis in this current cohort study. Our findings suggest that ASD patients with unknown etiology should be considered for methylation-specific PCR testing for Angelman syndrome where chromosomal microarray is not available. In the study, we also review the clinical features of Angelman syndrome caused by UPD and the frequency of ASD in individuals with Angelman syndrome.
自闭症谱系障碍（ASD）是一组病因异质性的神经发育障碍。染色体微阵列现已被推荐为ASD的一线临床诊断检测方法。我们使用Illumina HumanCytoSNP-12 v2.1阵列对16名泰国ASD患者进行了染色体微阵列检测，发现1例15号染色体单亲二体（UPD）。甲基化特异性PCR显示母源等位基因甲基化异常。单倍型分析显示该患者的两条15号染色体均来自其父亲。这些结果与天使综合征一致。然而，他的临床特征对典型的天使综合征并无临床意义。他2岁时首次在儿科诊所就诊，当时没有语言能力，社交互动技能差，有符合DSM-IV标准的ASD相关重复行为，5岁时经ADOS确诊。他明显超重，但没有畸形面容、癫痫发作或共济失调，被诊断为非综合征性ASD，直到10岁时，他的DNA被纳入本队列研究进行分析，此前一直维持这一诊断。我们的研究结果表明，对于病因不明的ASD患者，如果无法进行染色体微阵列检测，应考虑进行天使综合征的甲基化特异性PCR检测。在本研究中，我们还回顾了由UPD引起的天使综合征的临床特征以及天使综合征患者中ASD的发生率。
