Clinical and Molecular Studies of Achonddroplasia

本研究有三个具体目的：1）软骨发育不全发病和死亡原因的鉴定和表征，2）分子遗传学研究，旨在鉴定导致软骨发育不全和相关疾病的突变与受影响个体表型之间的相关性，并阐明其发病机制，3）分子遗传学研究，旨在鉴定其他FGFR 3疾病中的突变。一种新发现的骨骼发育不良，伴有严重软骨发育不全、发育迟缓和黑色素瘤（SADDAN），被发现是由特定的FGFR 3突变K650 M引起的。迄今为止，已在3例具有该表型的患者中发现了该突变。正在努力进一步确定临床表型，并阐明由K650 M突变引起的疾病的发病机制。与NICHD的Jeffrey Baron博士的合作研究已经确定了与全身性身材矮小相关的FGFR 3改变。这种改变，这已经发现在5例患者的日期，预计将改变一个已知的剪接位点。与NIDDK的Chuxia Deng博士合作，已经建立了II型致炎性发育不良和SADDAN表型的小鼠模型。- 软骨发育不全自然史软骨发育不全FGFR 3动物模型侏儒症骨骼发育不良致死性发育不良-人类受试者

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. - Achondroplasia Natural History Hypochondroplasia FGFR3 Animal Model dwarfism skeletal dysplasia thanatophoric dysplasia - Human Subjects