CONGENITAL CYTOMEGALOVIRUS RESEARCH

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 巨细胞病毒（CMV）是人类最常见的先天性感染，影响约1%的新生儿。虽然大多数CMV感染的婴儿在出生时没有症状，但大约10%的婴儿有严重的症状，并且可能高达15%的出生时没有症状的婴儿将在儿童后期发展出可检测到的感音神经性听力损失（SNHL）。在出生时有症状的人中，10%将在婴儿期死亡，幸存者将患有SNHL，智力迟钝，认知问题，视力障碍，行为问题或脑瘫。这些可变结果具有宿主和病毒决定因素，但尚未确定良好的预测标志物。我们实验室的初步数据表明，人类CMV编码的TNF α受体基因（UL 144）的多态性似乎与严重的先天性CMV结局相关。在23名先天性感染婴儿的队列中，我们发现具有罕见UL 144基因型的CMV感染与严重疾病高度相关（p 0.02）。其他研究小组认为，病毒（病毒载量）的数量可能会导致感染，患有严重疾病的婴儿的母亲羊水中的病毒载量很高。我们建议确定CMV基因型和病毒载量在严重疾病发展中的相对作用，主要通过听力损失来衡量。我们预计在2年内招募80例患者，并对每位患者进行至少2年的随访（总研究持续时间为4年）。每例受试者将从6个月大开始每6个月进行4次访视。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cytomegalovirus (CMV) is the most common congenital infection in humans, affecting roughly 1% of births. While most CMV-infected infants have no symptoms at birth, approximately 10% are severly symptomatic and it is possible that up to 15% of those with no symptoms at birth will develop sensorineural hearing loss (SNHL) detectable later in childhood. Of those who are symptomatic at birth, 10% will die in infancy, and the survivors will have SNHL, mental retardation, cognitive problems, visual impairement, behavioral problems, or cerebral palsy. These variable outcomes have host and viral determinants, but no good predictive markers have been identified. Preliminary data from our laboratory suggests that polymorphisms in the human CMV-encoded TNF alpha receptor gene (UL144) appear to correlate with severe congenital CMV outcome. In a cohort of 23 congenitally infected infants, we found that CMV infection with uncommon genotypes of UL144 was highly associated with severe disease (p 0.02). Other groups have suggested a role for the amount of virus (viral loads) causing infection, with high viral loads in the amniotic fluids of mothers of infants with severe disease. We propose to determine the relative role of CMV genotypes and viral loads in the development of severe disease primarily as measured by hearing loss. We anticipate recruiting 80 patients over 2 years and following each for a minimum of 2 years (total study duration 4 years). Each subject will have 4 visits every 6 months starting at age 6 months.