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Next-generation sequencing panel analysis in 24 Chinese patients with congenital ectopia lentis

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Abstract

Background

Congenital ectopia lentis (CEL) is a rare but serious disease. We use next-generation sequencing to detect genes associated with lens abnormalities in 24 patients with bilateral CEL and search for pathogenic genes and mutation sites.

Materials and methods

A total of 24 patients diagnosed with CEL from January 2019 to November 2019 were enrolled in this study, and their clinical data were collected and genome-wide deoxyribonucleic acid was extracted from peripheral venous blood. Targeted gene capture technology was used to obtain 188 exons of lens abnormality-related genes, which were sequenced using a high-throughput method. The mutation sites were determined through data analysis and verified by the Sanger method. According to the data from previous studies, the association between the genotype and clinical phenotype was analysed.

Result

Of the 24 patients, 23 had mutations in the fibrillin-1 (FBN1) gene, and 20 were diagnosed with Marfan syndrome. The 23 cases of FBN1 mutations were all heterozygous mutations, including 17 missense mutations, 3 splicing variants, 2 exon deletion mutations, 1 codon mutation, and 9 new mutations. A total of 17 mutations were located in the calcium-binding epidermal growth factor domain, including 16 mutations that contained missense mutations of cysteine. In addition, a heterozygous mutation of the gap junction protein alpha 8 (GJA8) gene was detected in one patient.

Conclusion

In this study, we identified 23 FBN1 gene mutations and 1 GJA8 gene mutation in 24 patients with CEL. Of these, 9 new FBN1 mutations and 14 known mutations were found. The results expanded the mutation spectrum of the FBN1 gene, suggesting that FBN1 mutation may be the main cause of CEL in Chinese patients.

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Funding

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Authors and Affiliations

  1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology & Visual Science Key Lab, Beijing Institute of Ophthalmology, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, China

    Meng Qi, Chong Wang, Yi Liu & Xiangyu Shi

  2. Department of Ophthalmology, Ningxia Eye Hospital, People′s Hospital of Ningxia Hui Autonomous Region, Huanghe Road, Jinfeng District, Yinchuan, 750002, the Ningxia Hui Autonomous Region, China

    WeiNing Rong

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  1. Meng Qi
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  2. Chong Wang
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  3. Yi Liu
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  4. Xiangyu Shi
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Correspondence to Xiangyu Shi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Beijing Tongren Hospital, Capital Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Qi, M., Wang, C., Liu, Y. et al. Next-generation sequencing panel analysis in 24 Chinese patients with congenital ectopia lentis. Int Ophthalmol 42, 2245–2253 (2022). https://doi.org/10.1007/s10792-022-02224-6

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  • DOI: https://doi.org/10.1007/s10792-022-02224-6

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