Wang Juan, Li Shiqiang, Xiao Xueshan, Wang Panfeng, Guo Xiangming, Zhang Qingjiong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China.
Mol Vis. 2010 Jun 22;16:1146-53.
To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1).
Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing.
Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness.
Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before.
检测中国1型瓦登伯革氏综合征（WS1）患者中配对盒基因3（PAX3）的突变及相关表型。
从我们的遗传性眼病基因组DNA库中选取5个疑似WS1的无关家系。通过聚合酶链反应扩增PAX3的编码区和相邻内含子区域，然后对扩增产物进行循环测序。对检测到的变异在可用的家系成员以及100名对照中进一步进行异源双链 - 单链构象多态性（异源双链 - SSCP）分析和/或克隆测序评估。
在5例患者中分别检测到3个PAX3的新突变和2个已知突变：c.567_586 + 17del（p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly）、c.456_459dupTTCC（p.Ile154PhefsX162）、c.795_800delCTGGTT（p.Trp266_Phe267del）、c.799T>A（p.Phe267Ile）和c.667C>T（p.Arg223X）。两个新突变被证明是新发的，因为其父母不携带这些突变。所有5例携带PAX3突变的患者均有内眦异位，两眼间虹膜颜色和眼底不同。然而，无一例有白色额发、皮肤色素减退和耳聋。
我们的研究结果扩展了中国WS1患者中PAX3突变的频率和谱以及与种族相关的表型。此前尚未报道过PAX3的新发突变。
