GENETIC STUDIES OF CRANIOFACIAL AND LIMB DISORDERS

颅缝融合是颅缝过早融合的一种常见症状。 导致头部形状异常的发育异常。在中等至 严重者，有颅内压升高和神经症状。 后遗症，如果不手术治疗的话。颅缝融合是强直性脊柱炎的一个特征。 多达50种遗传综合征。四肢畸形，如并指畸形和 指短指是这些疾病的常见相关特征。 Crouzon、Jackson-Weiss和Pfeiffer综合征是常染色体显性遗传， 颅缝融合病症的表现有很大的变异性。我们 确定了具有这些条件的家系来研究他们的染色体 和/或已建立的淋巴母细胞或成纤维细胞培养的DNA。 成纤维细胞生长因子受体2(FGFR2)突变已在 这些条件。 我们研究了39例患有这三种情况之一的FGFR2外显子111a。 或先前仅在Crouzon综合征中报道的外显子11lc也存在 出现在另外两种综合征中的一种。两个插入，一个在外显子111a中 Pfeiffer综合征患者的Crouzon综合征和外显子11lc的另一例 患者，均进行了观察。后一种突变具有相同的替代RNA 剪接效应是已报道的Crouzon综合征的同义突变。 在一家系中检测到错义突变V359F，其中一名成员患有 颅缝融合和宽趾，诊断Pfeiffer综合征，以及 有两个特征与Crouzon综合征一致的成员， 无肢体畸形的颅缝早闭。家庭间和家庭内 FGFR2突变表达的变异性表明这三个 被认为在临床上不同的证候反而具有代表性。 一系列相关的颅突融合症和数字障碍。

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.