JZUS - Journal of Zhejiang University SCIENCE

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 Yin^1,2, Xiao-yun Fang^1,2, Chong-fei Jin^1,2, Jin-fu Yin^1,2, Jin-yu Li^1,2, Su-juan Zhao^1,2, Qi Miao^1,2, Feng-wei Song^1,2
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

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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",
volume="15",
number="1",
pages="43-50",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300053"
}

%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

TY - JOUR
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

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: 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.

一种新的PITX2基因缺失/插入移码突变引起的Axenfeld-Rieger综合征研究

研究目的：对1个Axenfeld-Rieger综合征家系的临床特点及基因突变进行研究，探索Axenfeld-Rieger综合征发病的遗传机制。
研究手段：对该Axenfeld-Rieger综合征家系进行全面临床检查，对家系成员应用聚合酶链反应（PCR）扩增PITX2基因和FOXC1基因的所有外显子及相邻内含子，对其产物进行直接测序并对PITX2基因第5个外显子进行克隆测序。选取100名健康者作为对照组，应用PCR扩增PITX2基因第5个外显子并进行直接测序。应用SWISS-MODEL软件对野生型和突变型的PITX2蛋白同源域进行建模分析。
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。

关键词：Axenfeld-Rieger综合征；PITX2基因；FOXC1基因；移码突变；同源域

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一种新的PITX2基因缺失/插入移码突变引起的Axenfeld-Rieger综合征研究

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