GENETIC STUDIES OF CRANIOFACIAL AND LIMB DISORDERS

颅面和肢体疾病的遗传学研究

• 批准号: 6275462
• 负责人: Ethylin Wang Jabs
• 金额: $ 2.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6275462
• 关键词: autosomal dominant trait; child (0-11); clinical research; congenital skeletal disorder; craniofacial dysostosis; craniosynostosis; family genetics; fibroblast growth factor; gene mutation; genetic disorder diagnosis; genotype; growth factor receptors; human genetic material tag; human subject; orphan disease /drug; phenotype; syndrome

We studied 39 cases with one of these three conditions for FGFR2 exon 111a or exon 111c previously reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon 111a in a Crouzon syndrome patient and the other in exon 111c in a Pfeiffer syndrome patient, were observed. The latter mutation has the same alternative RNA splicing effect as a reported synonymous mutation for Crouzon syndrome. A missense mutation, V359F, was detected in a family with one member with craniosynostosis and broad digits, diagnostic of Pfeiffer syndrome, and with two members with features consistent with Crouzon syndrome, craniosynostosis without limb anomalies. The inter-and intrafamilial variability in expression of FGFR2 mutations suggests that these three syndromes, presumed to be clinically distinct, are instead representative of a spectrum of related craniosynostotic and digital disorders.

我们研究了39例这三种情况之一的FGFR 2外显子 111a或外显子111c先前仅在Crouzon综合征中报道， 也出现在另外两种综合征中。 两次插入，一次插入 Crouzon综合征患者的外显子111 a和另一个外显子111 c， Pfeiffer综合征患者。 后一种突变具有 与报告的同义突变相同的可变RNA剪接效应 克鲁松综合征的治疗方法 错义突变，V359F，检测到在一个， 一个有颅缝早闭和宽趾的家庭， 诊断Pfeiffer综合征，并与两名成员的特点 符合Crouzon综合征无肢颅缝早闭 异常 基因表达的家族间和家族内变异性 FGFR2突变表明，这三种综合征，假定是 临床上不同的，而是代表了一系列的 相关的颅缝早闭和指关节紊乱。