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

共 50 条

[31] A novel PAX3 mutation in a Korean patient with Waardenburg syndrome type 1 and unilateral branch retinal vein and artery occlusion: a case report
Eun Young Choi
Wungrak Choi
Christopher Seungkyu Lee
BMC Ophthalmology, 18
[32] Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in box domain of PAX3:: a simple variant or a true syndrome
Tekin, M
Bodurtha, JN
Nance, WE
Pandya, A
CLINICAL GENETICS, 2001, 60 (04) : 301 - 304
[33] A splice-site mutation affecting the paired box of PAX3 in a three generation family with Waardenburg syndrome type I (WS1)
Attaie, A
Kim, E
Wilcox, ER
Lalwani, AK
MOLECULAR AND CELLULAR PROBES, 1997, 11 (03) : 233 - 236
[34] Characterization of a novel missense mutation on murine Pax3 through ENU mutagenesis
Xiao, Yue
Zhang, Lingling
He, Kuanjun
Gao, Xiang
Yang, Lun
He, Lin
Ma, Gang
Guo, Xizhi
JOURNAL OF GENETICS AND GENOMICS, 2011, 38 (08) : 333 - 339
[35] Einseitige Innenohrschwerhörigkeit bei Mutationen im PAX3-Gen bei Waardenburg-Syndrom Typ IUnilateral sensineural deafness associated with mutations in the PAX3-gene in Waardenburg syndrome type I
M. Ptok
S. Morlot
HNO, 2006, 54 : 557 - 560
[36] Identification of nine novel variants across PAX3, SOX10, EDNRB, and MITF genes in Waardenburg syndrome with next-generation sequencing
Lee, Chen-Yu
Lo, Ming-Yu
Chen, You-Mei
Lin, Pei-Hsuan
Hsu, Chuan-Jen
Chen, Pei-Lung
Wu, Chen-Chi
Hsu, Jacob Shujui
MOLECULAR GENETICS & GENOMIC MEDICINE, 2022, 10 (12):
[37] A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report
Shi, Yunfang
Li, Xiaozhou
Ju, Duan
Li, Yan
Zhang, Xiuling
Zhang, Ying
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2016, 11 (04) : 1516 - 1518
[38] Functional analysis of a nonstop mutation in MITF gene identified in a patient with Waardenburg syndrome type 2
Sun, Jie
Hao, Ziqi
Luo, Hunjin
He, Chufeng
Mei, Lingyun
Liu, Yalan
Wang, Xueping
Niu, Zhijie
Chen, Hongsheng
Li, Jia-Da
Feng, Yong
JOURNAL OF HUMAN GENETICS, 2017, 62 (07) : 703 - 709
[39] A new missense mutation in the paired domain of the mouse Pax3 gene
Ohno, Tamio
Maegawa, Tomoki
Katoh, Hiroto
Miyasaka, Yuki
Suzuki, Miyako
Kobayashi, Misato
Hori, Fumihiko
EXPERIMENTAL ANIMALS, 2017, 66 (03) : 245 - 250
[40] Double heterozygous mutations of MITF and PAX3 result in Waardenburg syndrome with increased penetrance in pigmentary defects
Yang, T.
Li, X.
Huang, Q.
Li, L.
Chai, Y.
Sun, L.
Wang, X.
Zhu, Y.
Wang, Z.
Huang, Z.
Li, Y.
Wu, H.
CLINICAL GENETICS, 2013, 83 (01) : 78 - 82

← 1 2 3 4 5 →