Identification and functional analysis of a novel mutation in the PAX3 gene associated with Waardenburg syndrome type I

被引：8

作者：

Niu, Zhijie ^{[1
,2
]}

Li, Jiada ^{[3
]}

Tang, Fen ^{[4
]}

Sun, Jie ^{[1
,2
]}

Wang, Xueping ^{[1
,2
]}

Jiang, Lu ^{[1
,2
]}

Mei, Lingyun ^{[1
,2
]}

Chen, Hongsheng ^{[1
,2
]}

Liu, Yalan ^{[1
,2
]}

Cai, Xinzhang ^{[1
,2
]}

Feng, Yong ^{[1
,2
,3
]}

He, Chufeng ^{[1
,2
]}

机构：

[1] Cent S Univ, Xiangya Hosp, Dept Otolaryngol Head & Neck Surg, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[2] Key Lab Otolaryngol Major Dis Res Hunan Prov, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China

[4] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China

来源：

GENE | 2018年 / 642卷

基金：

中国国家自然科学基金;

关键词：

Mutation; PAX3; Waardenburg syndrome; Sensorineural hearing loss; Haploinsufficiency; PAIRED DOMAIN; DNA-BINDING; MITF; SOX10; HOMEODOMAIN; DISEASE;

D O I：

10.1016/j.gene.2017.11.035

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation. WS1 is due to loss-of-function mutations in paired box gene 3 (PAX3). Here, we identified a novel PAX3 mutation (c.808C > G, p.R270G) in a three-generation Chinese family with WS1, and then analyzed its in vitro activities. The R270G PAX3 retained nuclear distribution and normal DNA-binding ability; however, it failed to activate MITF promoter, suggesting that haploinsufficiency may be the underlying mechanism for the mild WS1 phenotype of the study family.

引用

页码：362 / 366

页数：5

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