Radoeva Petya D, Coman Ioana L, Salazar Cynthia A, Gentile Karen L, Higgins Anne Marie, Middleton Frank A, Antshel Kevin M, Fremont Wanda, Shprintzen Robert J, Morrow Bernice E, Kates Wendy R
Departments of aNeuroscience and Physiology bPsychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse cThe Virtual Center for Velo-Cardio-Facial Syndrome, Manlius dDepartment of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
Psychiatr Genet. 2014 Dec;24(6):269-72. doi: 10.1097/YPG.0000000000000062.
Velocardiofacial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for psychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. There is emerging evidence for the involvement of catechol-O-methyltransferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH) in the psychiatric phenotype of individuals with VCFS. Here, we tested the hypothesis that PRODH and COMT are associated with ASD in youths with VCFS. We found that individuals with VCFS and the low-activity alleles of both PRODH and COMT (rs4819756A and rs4680A) were more likely to present with ASD as compared with individuals with VCFS and the high-activity alleles of these genes [P<0.05; odds ratio=6.0 (95% confidence interval=1.27-28.26; N=87)]. Our results suggest that PRODH and COMT may interact to contribute to the ASD phenotype in individuals with VCFS.
腭心面综合征（VCFS；22q11.2缺失综合征）是一种由22号染色体q11.2区域半合子缺失导致的遗传性疾病，与包括自闭症谱系障碍（ASD）和精神分裂症在内的精神疾病风险大幅增加有关。越来越多的证据表明，儿茶酚-O-甲基转移酶（COMT）和脯氨酸脱氢酶（氧化酶）1（PRODH）与VCFS患者的精神表型有关。在此，我们检验了PRODH和COMT与VCFS青少年ASD相关的假说。我们发现，与具有这些基因高活性等位基因的VCFS患者相比，同时具有PRODH和COMT低活性等位基因（rs4819756A和rs4680A）的VCFS患者更易患ASD [P<0.05；优势比=6.0（95%置信区间=1.27 - 28.26；N=87）]。我们的结果表明，PRODH和COMT可能相互作用，促使VCFS患者出现ASD表型。
