Fragile X Syndrome: Banbury Conferences

描述（由申请人提供）：本提案请求支持班伯里脆弱X综合征会议（FXS）延续5年。包括首次会议在内，在纽约长岛冷泉港实验室的班伯里会议中心举行了六次这样的会议。我们建议每年召开5次关于脆性X综合征（fragile X syndrome， FXS）基础和临床研究的跨学科会议。这些会议旨在汇集广泛的科学家，包括从事FXS研究的科学家和其他相关领域的科学家。另一个目标是将年轻科学家，包括女性和少数族裔引入该地区。脆性X染色体综合征是最常见的智力迟钝的遗传原因。它是由于FMR-1基因的5'未翻译启动子区域中一个不稳定的三核苷酸重复区域的扩大，导致胞嘧啶残基的高甲基化，通常导致基因沉默。许多用于该综合征的小鼠FMR-1基因敲除模型已经或即将问世。脆性X智力迟钝蛋白（FMRP）的功能被认为是具有多种细胞功能的mrna亚群的转运和翻译调节。FMRP似乎在突触上翻译，以响应代谢性谷氨酸受体的激活。在人类和基因敲除小鼠模型中，在几个大脑区域的总体大小和突触的精细结构中，可以看到这种疾病的相对微妙的表型影响。正如班伯里会议明确指出的那样（在C部分总结），我们对这种疾病的认识正在迅速取得进展。没有其他专门针对FXS的基础和临床研究的会议，与会者一致认为班伯里会议非常有价值。

DESCRIPTION (provided by applicant): This proposal requests support for a 5 year continuation of the Banbury Conferences on Fragile X syndrome (FXS). Including an initial conference, six such meetings have been held at Banbury Conference Center at Cold Spring Harbor Laboratory on Long Island NY. We propose a series of five annual interdisciplinary conferences on basic and clinical research relevant to fragile X syndrome (FXS). The conferences are intended to bring together a broad range of scientists, both those working on FXS and others in allied, relevant fields. Another goal is to introduce young scientists, including females and minorities, to the area. Fragile X syndrome is the most common inherited cause of mental retardation. It arises due to expansion of an unstable region of trinucleotide repeats in the 5' untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine residues and, generally, silencing of the gene. A number of mouse FMR-1 knockout models for the syndrome have or are about to become available. The function of the fragile X mental retardation protein (FMRP) is believed to be the transport and translational regulation of a subset of mRNAs with a diverse set of cellular functions. FMRP appears to be translated at synapses in response to activation of metabotropic glutamate receptors. Relatively subtle phenotypic effects of the disorder are seen in the gross size of several brain regions and in the fine structure of synapses in humans and in the knockout mouse model. As the Banbury Conferences have made clear (summarized in Sec. C), advances in our knowledge of this disorder are occurring very rapidly. There is no other meeting devoted exclusively to basic and clinical research on FXS, and the participants consistently report the Banbury Conference to be extremely valuable.