Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Autism Res. 2014 Apr;7(2):254-63. doi: 10.1002/aur.1365. Epub 2014 Mar 13.
CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression-previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister.
CD38 编码催产素信号通路中的配体。该基因中的一些单核苷酸多态性与自闭症谱系障碍（ASD）患者的低血清催产素水平有关。基于动物研究，催产素的破坏被假设可以解释 ASD 的特征，包括沟通和社交行为受损。最近的人类研究表明，催产素的给药可以改善 ASD 患者的情绪识别、促进社交行为，并改善对社交刺激的听觉处理。除了在催产素信号中的作用外，CD38 还参与调节气道平滑肌中的钙浓度，CD38 的功能障碍与哮喘等气道疾病有关。虽然许多研究表明罕见的染色体缺失和重复有助于确定自闭症的遗传风险，但据我们所知，没有关于描述 ASD 患者中涉及 CD38 或缺失的重排的报告。在这里，我们介绍了两位被诊断患有自闭症的姐妹，她们有回归的特征——在生命的第二年失去了以前获得的言语。妹妹也患有哮喘，继承了母亲的 4p15.32 缺失，导致 BST1-CD38 融合转录本。她们母亲的缺失是镶嵌性的，她没有受到影响。尽管需要进一步的工作来评估融合转录本的功能后果，但我们假设先证者的缺失可能是自闭症的一个风险因素，当与其他易感变异结合时，导致比她的妹妹更严重的表现。
