中文摘要：

目的对1个汉族先天性眼外肌纤维化2型（congenital fibrosis of extraocular muscles type2，CFEOM2）家系进行连锁分析和突变筛查，以确定该家系的致病基因。方法收集该家系2代中的5例患者以及7名正常成员。进行详细的眼科检查，并提取外周血基因组DNA。选用ABIPRISM LinkageMapping Set-MD10染色体标记物对已知基因PHOX2A（又名ARIX基因）侧翼位点D11S4151和D11S1320进行扫描。确定连锁之后，对候选基因PHOX2A的外显子进行直接测序。结果在该家系中，D11S4151和D11S1320微卫星标记物与PHOX2A基因存在连锁。测序结果显示，PHOX2A基因第2外显子存在227T→G突变，导致N76K氨基酸替换。该突变位于PHOX2A基因高度保守区域，导致编码蛋白的结构发生明显变化。突变蛋白由于磷酸化识别位点改变而影响了自身的磷酸化。结论PHOX2A基因227T→G突变是该家系眼外肌纤维化发病的分子基础。

英文摘要：

Objective To investigate potential mutation of PHOX2A （or ARIX） gene in a Chinese family affected with congenital fibrosis of extraocular muscles tyep 2 （CFEOM2）. Methods Genomic DNA was obtained from affected and unaffected members of the family. With an ABI PRSIM Linkage Mapping Set-MD10 kit, selected markers flanking the PHOX2A locus were used for linkage analysis. Exons of PHOX2A gene were amplified and sequenced. A total of 100 normal subjects were recruited as controls. Results Genetic linkage was found at llq13 between DllS4151 and DllS1320 and the PHOX2A gene. DNA sequencing has identified a heterozygous mutation in the exon 2 of the gene （227T→G, N76K）. The same mutation was not found in the unaffected and 100 normal controls. Conclusion A mutation of the PHOX2A gene 227T→G is responsible for the onset of congenital fibrosis of extraocular muscles type 2 in this Chinese family.