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Objective <p>This study aimed to investigate the pathogenic gene mutation associated with high myopia and congenital stationary night blindness (CSNB) in a family from Northeast China. The objective was to clarify the underlying genetic basis and to determine the inheritance pattern of these ocular disorders.</p> Methods <p>Whole-exome sequencing was performed on the proband using the NovaSeq 6000 platform. Variants were filtered based on an allele frequency of less than 0.5% in the gnomAD database. Their pathogenic was evaluated using multiple in silico prediction tools, including CADD, REVEL, SpliceAI, SIFT, MutationTaster, PolyPhen-2, and AlphaMissense. The identified <i>NYX</i> mutation was subsequently validated through Sanger sequencing in the proband and six additional family members. In addition, comprehensive clinical evaluations were conducted. These included detailed ophthalmic examinations, assessment of refractive status, and fundus imaging. These investigations were performed to characterize the phenotypic features and to establish correlations with the genetic findings.</p> Results <p>A novel frameshift mutation, c.264dup p. (Arf89Alafs *26), was identified in exon 3 of the NYX gene. The proband exhibited extremely high myopia, with a spherical equivalent of less than − 23.00D. This condition was accompanied by typical clinical features of CSNB. Structural analysis indicated significant conformational changes in the mutant protein. Pedigree analysis supported an X-linked recessive mode of inheritance. This pattern was consistent with both the clinical presentation and the genetic findings observed in the affected family.</p> Conclusion <p>This study is the first to identify the <i>NYX</i> c.264dup mutation as a causative variant of complete CSNB (cCSNB) accompanied by extreme high myopia. This finding expands the known mutational spectrum of the <i>NYX</i> gene. These results provide valuable evidence for improving molecular diagnostic strategies. They also offer important support for more accurate genetic counseling in affected individuals and their families.</p>

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A novel NYX gene mutation identified in a Chinese Northeast Han family with high myopia and night blindness

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Xiaoyi Xu,
  • Liwen Zhang,
  • Ying Li,
  • Lili Dai,
  • Zheng Xiao,
  • Dongqi Yao

摘要

Objective

This study aimed to investigate the pathogenic gene mutation associated with high myopia and congenital stationary night blindness (CSNB) in a family from Northeast China. The objective was to clarify the underlying genetic basis and to determine the inheritance pattern of these ocular disorders.

Methods

Whole-exome sequencing was performed on the proband using the NovaSeq 6000 platform. Variants were filtered based on an allele frequency of less than 0.5% in the gnomAD database. Their pathogenic was evaluated using multiple in silico prediction tools, including CADD, REVEL, SpliceAI, SIFT, MutationTaster, PolyPhen-2, and AlphaMissense. The identified NYX mutation was subsequently validated through Sanger sequencing in the proband and six additional family members. In addition, comprehensive clinical evaluations were conducted. These included detailed ophthalmic examinations, assessment of refractive status, and fundus imaging. These investigations were performed to characterize the phenotypic features and to establish correlations with the genetic findings.

Results

A novel frameshift mutation, c.264dup p. (Arf89Alafs *26), was identified in exon 3 of the NYX gene. The proband exhibited extremely high myopia, with a spherical equivalent of less than − 23.00D. This condition was accompanied by typical clinical features of CSNB. Structural analysis indicated significant conformational changes in the mutant protein. Pedigree analysis supported an X-linked recessive mode of inheritance. This pattern was consistent with both the clinical presentation and the genetic findings observed in the affected family.

Conclusion

This study is the first to identify the NYX c.264dup mutation as a causative variant of complete CSNB (cCSNB) accompanied by extreme high myopia. This finding expands the known mutational spectrum of the NYX gene. These results provide valuable evidence for improving molecular diagnostic strategies. They also offer important support for more accurate genetic counseling in affected individuals and their families.