CLINICAL AND MOLECULAR STUDIES OF ACHONDROPLASIA

这项研究有三个具体目的：1) 确定和描述发病和死亡的原因 软骨发育不全的死亡率，2)分子遗传学研究设计 以确定导致 软骨发育不全和相关疾病及其表型 个体，并阐明其发病机制；3)分子 旨在识别其他FGFR3突变的基因研究 精神错乱。一种新发现的骨骼发育不良，严重 软骨发育不全、发育迟缓与黑棘皮病 (SADDAN)，已被发现由特定的FGFR3引起 突变，K650M。到目前为止，已在3例中发现了这种突变 有这种表型的患者。目前正在努力进一步界定 本病的临床表型及发病机制 由K650M突变引起的疾病。协作研究，与 NICHD的杰弗里·巴伦博士发现了一种FGFR3突变 与普遍的矮小有关。这一变化，它具有 到目前为止已在5名患者中发现，预计将改变已知的剪接 地点。矮小的发病机制至少在一定程度上导致 这一变化的原因正在调查中。与Dr. NIDDK的邓楚霞，胸腺性发育不良小鼠模型 类型II和SADDAN表型已经创建。

This study has three specific aims: 1) the identification and characterization of causes of morbidity and mortality in achondroplasia, 2) molecular genetic studies designed to identify correlations between mutations which cause achondroplasia and related disorders and the phenotypes of affected individuals, and elucidate their pathogenesis, and 3) molecular genetic studies designed to identify mutations in other FGFR3 disorders. A newly identified skeletal dysplasia, with Severe Achondroplasia, Developmental Delay and Acanthosis Nigricans (SADDAN), has been found to result from a specific FGFR3 mutation, K650M. To date, the mutation has been found in 3 patients with this phenotype. Efforts are underway to further define the clinical phenotype and elucidate the pathogenesis of the disorder caused by the K650M mutation. Collaborative studies with Dr. Jeffrey Baron of NICHD have identified an FGFR3 alteration associated with generalized short stature. This alteration, which has been found in 5 patients to date, is predicted to alter a known splice site. The pathogenesis of short stature resulting, at least in part, from this alteration is under investigation. In collaboration with Dr. Chuxia Deng of NIDDK, mouse models for thantophoric dysplasia type II and the SADDAN phenotype have been created.