FGFR2突变位点Ser252Trp与Pro253Arg对Apert综合征临床表型影响的差异—基于荟萃分析的证据

目的探索Apert综合征患者中两个常见突变Ser252Trp和Pro253Arg对临床表型影响的差异。方法分别以"Apert and FGFR2"、"Apert综合征和FGFR2突变"为关键词,在PubMed和中国知网中进行检索,从227篇文献中筛选出29篇同时包含FGFR2基因突变和临床表型的文章。本研究的样本量为230例Apert综合征患者,涉及37种临床表型。其中男女比率为1∶1,平均年龄为(8.9±9.6)岁。利用t检验、卡方检验或Fisher精确检验,比较两个突变(Ser252Trp和Pro253Arg)之间临床表型的差异。结果 87%的患者能检测到FGFR2基因上的Ser252Trp和Pro253Arg两个常见突变,低于之前报道的98%。其中伴发腭裂的频率,Ser252Trp突变约为Pro253Arg突变的2.3倍(55%vs 24%,P<0.001);Pro253Arg突变中Ⅲ型并指发生频率显著高于Ser252Trp突变(69%vs 29%,P<0.001);其他临床表型在两个突变中的差异不具有统计学意义。结论本研究通过整合1995年至2017年间的相关文献,发现Apert综合征中两个常见突变的发生频率可能存在一定程度的高估;两个突变之间的表型影响具有细微差异,两者相较,Ser252Trp突变者较常出现腭裂畸形,而Pro253Arg突变则会出现较为严重的并指畸形。

Differences in the Clinical Phenotypes of Apert Syndrome with the FGFR2 Mutation Site Ser252Trp and Pro253Arg: Based on Meta Analysis

Objective To explore the differences in the phenotypic effects of two common mutations (Ser252Trp and Pro253Arg) in patients with Apert syndrome. Methods The key terms "Apert and FGFR2", "Apert syndrome and FGFR2 mutation" were retrieved in PubMed and CNKI databases respectively, and 29 literatures containing gene mutations and clinical phenotypes were selected from 227 articles. A total of 230 cases were reported, involving 37 clinical manifestations. The male to female ratio was 1:1, and the average age was 8.9±9.6 years. The correlation between clinical phenotypes and gene mutations were compared by t test, chi square test or Fisher's exact test. Results The two common mutations were detected in 87% of our patients with Apert syndrome, lower than the previously reported 98% level. The frequency of cleft palate in Ser252Trp was 2.3 times as high as that in Pro253Arg (55% vs 24%, P<0.001), and the frequency of type Ⅲsyndactyly(hands)in Pro253Arg was significantly higher than that in Ser252Trp(69% vs 29%,P<0.001),while there was no significant difference in other clinical manifestations between the two mutations. Conclusion According to the relevant literatures during 1995-2017, the frequency of two common mutations in Apert syndrome may be overestimated. There are subtle differences in the clinical phenotypes between two mutations in the Apert syndrome. Cleft palate is significantly more common in patients with the Ser252Trp mutation. In contrast, the syndactyly for hands is more severe in patients with the Pro253Arg mutation.