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CLC number: R774.1

On-line Access: 2014-01-04

Received: 2013-02-23

Revision Accepted: 2013-07-01

Crosschecked: 2013-12-27

Cited: 4

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Citations:  Bibtex RefMan EndNote GB/T7714

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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.1 P.43-50


Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome* #

Author(s):  Hou-fa Yin1,2, Xiao-yun Fang1,2, Chong-fei Jin1,2, Jin-fu Yin1,2, Jin-yu Li1,2, Su-juan Zhao1,2, Qi Miao1,2, Feng-wei Song1,2

Affiliation(s):  1. Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   xiaoyun.fang@aliyun.com

Key Words:  Axenfeld-Rieger syndrome, PITX2 gene, FOXC1 gene, Frameshift mutation, Homeodomain

Hou-fa Yin, Xiao-yun Fang, Chong-fei Jin, Jin-fu Yin, Jin-yu Li, Su-juan Zhao, Qi Miao, Feng-wei Song. Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome[J]. Journal of Zhejiang University Science B, 2014, 15(1): 43-50.

@article{title="Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome",
author="Hou-fa Yin, Xiao-yun Fang, Chong-fei Jin, Jin-fu Yin, Jin-yu Li, Su-juan Zhao, Qi Miao, Feng-wei Song",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome
%A Hou-fa Yin
%A Xiao-yun Fang
%A Chong-fei Jin
%A Jin-fu Yin
%A Jin-yu Li
%A Su-juan Zhao
%A Qi Miao
%A Feng-wei Song
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 1
%P 43-50
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300053

T1 - Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome
A1 - Hou-fa Yin
A1 - Xiao-yun Fang
A1 - Chong-fei Jin
A1 - Jin-fu Yin
A1 - Jin-yu Li
A1 - Su-juan Zhao
A1 - Qi Miao
A1 - Feng-wei Song
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 1
SP - 43
EP - 50
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300053

Objective: axenfeld-Rieger syndrome (ARS) is phenotypically and genetically heterogeneous. In this study, we identified the underlying genetic defect in a Chinese family with ARS. Methods: A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 (PITX2) gene and the forkhead box C1 (FOXC1) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results: Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c.198_201delinsTTTCT (p.M66Ifs*133) was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions: We detected a novel frameshift mutation p.M66Ifs*133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been reported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.


重要结论:该Axenfeld-Rieger综合征家系的眼部表型多样,但是各患者的全身系统异常却呈现一致性(见图2;表1)。基因测序结果显示先证者及其他患者均具有PITX2基因杂合突变c.198_201delins TTTCT (p.M66Ifs*133)。尽管PITX2基因突变引起Axenfeld-Rieger综合征已经被广泛证实,但是PITX2基因缺失/插入移码突变引起的Axenfeld-Rieger综合征仅被报道过一次,我们的研究首次在中国人群中揭示了这种罕见的突变方式。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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