Clinical variability in patients with Apert's syndrome
Clinical variability in patients with Apert's syndrome
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DOI：
10.3171/jns.1999.90.3.0443
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发表时间：
1999-03-01
影响因子：
4.1
通讯作者：
Renier, D
中科院分区：
文献类型：
--
作者：
Lajeunie, E;Cameron, R;Renier, D
Object. Apert综合征的特征是面颅缝早闭和四肢严重的骨性和皮肤并指。这种综合征的分子基础似乎非常特异：两个相邻的氨基酸取代（S252 W或P253 R）发生在成纤维细胞生长因子受体（FGFR）2基因的第二和第三免疫球蛋白结构域之间的连接区。本研究的目的是检测Apert综合征患者的表型/基因型相关性。在本研究中，对36例Apert综合征患者进行了基因突变筛查。在所有病例中均检测到突变。在其中一名患者中，有一种罕见的突变，由同一密码子（S252 F）中的双碱基对取代组成。对我们的病例进行了表型调查，显示了这种综合征的临床变异性。在两名患者中，没有临床或放射学证据的颅缝早闭。在另外2例非典型并指畸形和颅骨畸形患者中，检测到特异性突变有助于诊断。P253 R突变似乎与更严重的形式有关，涉及并指畸形的形式和精神结果。在Apert综合征患者中发现的突变通常局限于FGFR 2外显子的特定区域，这一事实可能有助于诊断，并允许在困难的情况下进行遗传咨询。
Object. Apert's syndrome is characterized by faciocraniosynostosis and severe bony and cutaneous syndactyly of all four limbs. The molecular basis for this syndrome appears remarkably specific: two adjacent amino acid substitutions (either S252W or P253R) occurring in the linking region between the second and third immunoglobulin domains of the fibroblast growth factor receptor (FGFR)2 gene. The goal of this study was to examine the phenotype/genotype correlations in patients with Apert's syndrome.Methods. In the present study, 36 patients with Apert's syndrome were screened for genetic mutations. Mutations were detected in all cases. In one of the patients there was a rare mutation consisting of a double-base pair substitution in the same codon (S252F). A phenotypical survey of our cases was performed and showed the clinical variability of this syndrome. In two patients there was no clinical or radiological evidence of craniosynostosis. In two other patients with atypical forms of syndactyly and cranial abnormalities, the detection of a specific mutation was helpful in making the diagnosis.Conclusions. The P253R mutation appears to be associated with the more severe forms, with regard to the forms of syndactyly and to mental outcome. The fact that mutations found in patients with Apert's syndrome are usually confined to a specific region of the FGFR2 exon ma may be useful in making the diagnosis and allowing genetic counseling in difficult cases.