GENETIC STUDIES OF CRANIOFACIAL AND LIMB DISORDERS

颅缝早闭，颅骨缝过早融合，是一种常见的 导致头部形状异常的发育异常。 治疗中度至 严重者，颅内压增高，神经系统损害 后遗症，如果不手术治疗。 颅缝早闭是as的一个特征 多达50种遗传综合征 肢体异常，如并指和 短指畸形是这些病症的共同相关特征。 Crouzon、Jackson-Weiss和Pfeiffer综合征为常染色体显性遗传， 颅缝早闭病症，具有广泛的表达变异性。 我们 确定具有这些条件的家庭，以研究其染色体 和/或来自已建立的淋巴母细胞或成纤维细胞培养物的DNA。 成纤维细胞生长因子受体2（FGFR2）突变已在 了以下条件 我们研究了39例FGFR 2外显子IIIa的这三种情况之一， 或外显子IIlc以前只报道在Crouzon综合征也存在 其他两种综合症中的一种 两个插入，一个在外显子IIIa中， Crouzon综合征患者和Pfeiffer综合征的外显子IIIc中的另一个 病人，观察。 后一种突变具有相同的替代RNA 剪接效应是Crouzon综合征的同义突变。 在一个家系中检测到一个错义突变V359F， 颅缝早闭和宽趾，诊断为普发综合征，以及 有两个成员的特征符合Crouzon综合征， 颅缝早闭无肢体畸形。家庭内部和家庭内部 FGFR2突变表达的变异性表明，这三种突变都可能导致FGFR2突变。 综合征，假定是临床上不同的，而是代表性的， 一系列相关的颅缝早闭症和指关节紊乱

Craniosynostosis, the premature fusion of calvarial sutures, is a common developmental anomaly that causes abnormal head shape. In moderate to severe cases, there is increase intracranial pressure and neurological sequelae, if not surgically treated. Craniosynostosis is a feature of as many as 50 genetic syndromes. Limb abnormalities, such as syndactyly and brachydactyly, are common associated features of these conditions. Crouzon, Jackson-Weiss, and Pfeiffer syndromes are autosomal dominant, craniosynostotic conditions with a wide variability of expression. We ascertained families with these conditions to study their chromosomes and/or DNA from established lymphoblastoid or fibroblast cell cultures. Fibroblast growth factor receptor 2 (FGFR2) mutations have been found in these conditions. We studied 39 cases with one of these three conditions for FGFR2 exon llla or exon lllc previously reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon llla in a Crouzon syndrome patient and the other in exon lllc 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 member 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.