Clinical features and gene detection analysis in a family with congenital aniridia

Weihou LI; Danning LIU

doi:10.16016/j.2097-0927.202308087

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Clinical features and gene detection analysis in a family with congenital aniridia

Clinical Medicine | 更新时间：2026-01-09

- Clinical features and gene detection analysis in a family with congenital aniridia
- Journal of Army Medical University Vol. 46, Issue 11, Pages: 1277-1283(2024)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院眼科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202308087
  CLC： R394.2;R771.1;R773.1
- Received：23 August 2023，
  
  Revised：2023-11-08，
  
  Published：15 June 2024
- 稿件说明：
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Weihou LI, Danning LIU. Clinical features and gene detection analysis in a family with congenital aniridia[J]. Journal of Army Medical University, 2024, 46(11): 1277-1283.
DOI：

Weihou LI, Danning LIU. Clinical features and gene detection analysis in a family with congenital aniridia[J]. Journal of Army Medical University, 2024, 46(11): 1277-1283. DOI： 10.16016/j.2097-0927.202308087.

摘要

目的

分析先天性无虹膜1家系遗传学特点，了解

PAX

6基因突变特点及临床表型的差异。

方法

收集该家系的病史及临床资料，进行全外显子基因测序检查及数据分析，应用同源建模服务器SWISS-MODEL构建对应的蛋白质模型进行分析。

结果

本家系中4名发病者均因虹膜缺失存在畏光、睁眼困难症状，相同临床表型为无虹膜、白内障、黄斑中心凹发育不良，还存在个体差异表型。基因检测结果显示：4名发病者均为

PAX

6基因上c.442_452del: p.M148Afs*48的杂合缺失移码变异，该变异在物种间高度保守。同源建模结果提示突变的

PAX

6基因最终导致蛋白质构象发生差异变化。

结论

新发现的

PAX

6基因变异在发病的家系成员中表型不完全相同，通过同源建模分析增加了对

PAX

6异常表达导致蛋白质结构异常的认识，遗传学检查可对该家系提供遗传学证据。

Abstract

Objective

To analyze the genetic features of congenital aniridia in a family and to explore the characteristics of PAX6 gene mutations and differences in clinical phenotypes.

Methods

The medical history and clinical data of this family line were collected. Whole-exon gene sequencing and data analysis were performed

and homology modelling server SWISS-MODEL was applied to construct the corresponding protein model for analysis.

Results

All 4 individuals with onset in this family line had photophobia and difficulty in opening the eyes due to iris deficiency

with the same clinical phenotypes of aniridia

cataracts

and macular centro-concave dysplasia. But

there were still individual differences in phenotypes. Genetic examination showed that all 4 affected individuals were heterozygous for a heterozygous deletion shifted variant c.442_452del: p.M148Afs*48 on the PAX6 gene

which is highly conserved among species. Homozygous modeling suggested that the mutated PAX6 gene ultimately led to differential changes in protein conformation.

Conclusion

The newly identified PAX6 gene variant is not phenotypically identical among members of the family with congenital aniridia

and homology modeling analysis has increased the understanding that aberrant expression of PAX6 leads to structural abnormalities in the protein. Genetic examination may provide genetic evidence for this family line.

关键词

Keywords

references

BREMOND-GIGNAC D. Congenital aniridia in children[J]. Rev Prat, 2019, 69(1): 67-70.

TRIPATHY K, SALINI B. Aniridia[M]. Treasure Island: StatPearls Publishing, 2023.

GALINSKY V L. YOABS: yet other aligner of biological sequences—an efficient linearly scaling nucleotide aligner[J]. Bioinformatics, 2012, 28(8): 1070-1077. DOI: 10.1093/bioinformatics/bts102.

ULINTZ P J, WU W S, GATES C M. Bioinformatics analysis of whole exome sequencing data[J]. Methods Mol Biol, 2019, 1881: 277-318. DOI: 10.1007/978-1-4939-8876-1_21.

MILLER D T, LEE K, CHUNG W K, et al . ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)[J ] . Genet Med, 2021, 23(8): 1381-1390. DOI: 10.1038/s41436-021-01172-3.

RIGGS E R, ANDERSEN E F, CHERRY A M, et al . Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J ] . Genet Med, 2020, 22(2): 245-257. DOI: 10.1038/s41436-019-0686-8.

SUN H F, QIN B, LIU T, et al . CistromeFinder for ChIP-seq and DNase-seq data reuse[J ] . Bioinformatics, 2013, 29(10): 1352-1354. DOI: 10.1093/bioinformatics/btt135.

WU C, YANG J, ZHANG S Y, et al . A novel NCSTN gene mutation in a Chinese family with acne inversa[J ] . Mol Genet Genomics, 2018, 293(6): 1469-1475. DOI: 10.1007/s00438-018-1475-9..

KAVIRAJ M, KUMAR U, NAYAK A K, et al . Homology modeling and virtual characterization of cytochrome c nitrite reductase (NrfA) in three model bacteria responsible for short-circuit pathway, DNRA in the terrestrial nitrogen cycle[J ] . World J Microbiol Biotechnol, 2022, 38(10): 1-15. DOI: 10.1007/s11274-022-03352-y.

Richards S, Aziz N, Bale S, et al . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J ] . Genet Med. 2015;17(5): 405-42 4. DOI: 10.1038/gim.2015.30.

VASILYEVA T A, MARAKHONOV A V, KUTSEV S I, et al . Relative frequencies of PAX 6 mutational events in a Russian cohort of aniridia patients in comparison with the world's population and the human genome[J ] . Int J Mol Sci, 2022, 23(12): 6690. DOI: 10.3390/ijms23126690..

OUYANG J, CAI Z Y, GUO Y B, et al . Detection of a novel PAX6 variant in a Chinese family with multiple ocular abnormalities[J ] . BMC Ophthalmol, 2022, 22(1): 28.

TIBREWAL S, RATNA R, GOUR A, et al . Clinical and molecular aspects of congenital aniridia-A review of current concepts[J ] . Indian J Ophthalmol, 2022, 70(7): 2280. DOI: 10.4103/ijo.ijo_2255_21.

HINGORANI M, WILLIAMSON K A, MOORE A T, et al . Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations[J ] . Invest Ophthalmol Vis Sci, 2009, 50(6): 2581-2590. DOI: 10.1167/iovs.08-2827.

丛日昌, 宋书娟, 刘英芝. 先天性无虹膜症家系的基因突变位点研究[J]. 中华眼科杂志, 2006, 42(12): 1113-1117. DOI: 10.3760/j:issn:0412-4081.2006.12.012.

CONG R C, SONG S J, LIU Y Z. Study of genetic mutation locus in a family with congenital aniridia[J]. Chin J Ophthalmol, 2006, 42(12): 1113-1117. DOI: 10.3760/j:issn:0412-4081.2006.12.012.

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