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New splice site mutations in MYO7A causing Usher syndrome type 1: a study on a Chinese consanguineous family

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Abstract

Purpose

This study investigated the new splice site mutations of Myosin VIIA (MYO7A) in patients with Usher syndrome type 1 (USH1) from a three-generation Chinese consanguineous family.

Methods

All subjects underwent comprehensive ophthalmic examinations and an audiometric test. Demographic data, family history, and peripheral blood leukocytes were collected. We performed whole exome sequencing (WES) to analyze the genomic DNA of the family. DNA sequence and restriction fragment length polymorphism (RFLP) analyses were also done. The identified genetic variants were validated by conducting polymerase chain reaction (PCR) in 100 healthy control subjects and comparing with the NCBI VARIANT database and the 1000 Genomes Project. The functional consequences were further analyzed.

Results

WES identified two new splice site mutations (c.5648G > A(rs111033215) and c.6238-1G > C) in MYO7A in two patients with USH1, i.e., the proband and her elder brother. DNA sequence and RFLP analyses showed that other members without USH1 carried only one of the two mutations. In the analysis of healthy controls, neither mutation existed. Both mutations were predicted to be damaging and were most likely associated with USH1.

Conclusion

In the three-generation Chinese consanguineous family with USH1, c.5648G > A(rs111033215) and c.6238-1G > C mutations in MYO7A are most likely associated with the disease. Our findings expand the mutational spectrum of MYO7A, which will enhance the understanding of the genetic abnormalities in USH1 and provide more evidence for future investigations on therapeutic strategies such as precise gene replacement or gene editing.

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Data availability

The datasets generated and analyzed during the current study are available in the NCBI ClinVar repository, ClinVar accession number: SCV002510626, SCV002508889.

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Acknowledgements

We thank Medjaden Inc for scientific editing of this manuscript.

Funding

The authors have not disclosed any funding.

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Authors and Affiliations

  1. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, No. 83 Fenyang Road, Xuhui District, Shanghai, 200031, China

    Qinghong Lin, Dong Yang & Xingtao Zhou

  2. Refractive Surgery Department, Bright Eye Hospital, Shanghai, 200000, China

    Qinghong Lin & Zhengwei Shen

  3. NHC Key Laboratory of Myopia (Fudan University), Shanghai, China

    Qinghong Lin, Dong Yang & Xingtao Zhou

  4. Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China

    Qinghong Lin, Dong Yang & Xingtao Zhou

  5. Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China

    Qinghong Lin, Dong Yang & Xingtao Zhou

  6. Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000), Shanghai, China

    Qinghong Lin, Dong Yang & Xingtao Zhou

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  1. Qinghong Lin
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  2. Dong Yang
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Contributions

QL and XZ: data curation; formal analysis; writing—original draft. DY: investigation; methodology; project administration. ZS: Software. XZ: Writing—review and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xingtao Zhou.

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Conflict of interest

The authors declare no competing interests.

Ethics approval

This study was approved by the institutional review board of the Eye and ENT Hospital of Fudan University (Shanghai, China), and was conducted in compliance with the Declaration of Helsinki.

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Written informed consent was obtained from all individual participants included in the study.

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Lin, Q., Yang, D., Shen, Z. et al. New splice site mutations in MYO7A causing Usher syndrome type 1: a study on a Chinese consanguineous family. Int Ophthalmol 43, 2091–2099 (2023). https://doi.org/10.1007/s10792-022-02611-z

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  • DOI: https://doi.org/10.1007/s10792-022-02611-z

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