Case Report: A novel intronic FRMD7 variant associated with X-linked infantile nystagmus: functional validation by a minigene splicing assay
8 affiliations
- 1Department of Respiratory Intervention, Children’s Hospital Affiliated to Shandong University
- 2Institute of Pediatric Research, Children’s Hospital Affiliated to Shandong University
- 3Department of Laboratory, Affiliated Hospital of Shandong Traditional Chinese Medicine University
- 4Department of Laboratory, Children’s Hospital Affiliated to Shandong University
- 5School of Pharmacy, Binzhou Medical University
- 6Department of Ultrasound, Children’s Hospital Affiliated to Shandong University
- 7Department of Administrative Management, Children’s Hospital Affiliated to Shandong University
- 8College of Pharmacy, Shandong University of Traditional Chinese Medicine
Abstract
The X-linked ocular motor disorder known as FRMD7 associated infantile nystagmus syndrome: X-linked congenital nystagmus type 1 (NYS1; OMIM 310700) is typified by involuntary conjugate ocular oscillations starting in early infancy, typically without significant structural ocular abnormalities. Several infantile nystagmus waveforms are linked to pathogenic FRMD7 variants, which impair ocular motor development. A subset of affected individuals has been reported to exhibit periodic alternating nystagmus. In our clinical practice, we identified a male infant with nystagmus and conducted comprehensive testing on him and his parents. The proband exhibited persistent nystagmus at 1 months old and gradually worsened. Whole-exome sequencing revealed a novel intronic variant, c.206-9T>G in the FRMD7 gene (NM_194277.3) inherited from his unaffected mother. Pathogenicity analysis via minigene splicing assays demonstrated that the c.206-9T>G variant caused exon 4 (79 bp) skipping at the mRNA level. Based on the patient’s clinical features and functional validation of the genetic variant, the infant was diagnosed as X-linked congenital nystagmus type 1 (OMIM: 310700). The intronic variant c.206-9T>G happened in FRMD7 gene was verified pathogenic by minigene assay, and the study further broadened the mutational spectrum of FRMD7 and providing a molecular basis for genetic counseling for NYS1.
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BibTeX
@article{ma2026case,
title = {{Case Report: A novel intronic FRMD7 variant associated with X-linked infantile nystagmus: functional validation by a minigene splicing assay}},
author = {Jing Ma and Yanan Yang and Zhihao Shao and Dandan Qin and Xiaowei Chi and Hongmei Xin and Yue Jiang and Haozheng Zhang and Qinghua Liu and Qin Dong and Lijuan Zhang and Kaihui Zhang and Guohua Liu},
journal = {Frontiers in Neurology},
year = {2026},
month = nov,
doi = {10.3389/fneur.2026.1977906},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1977906/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: A novel intronic FRMD7 variant associated with X-linked infantile nystagmus: functional validation by a minigene splicing assay
AU - Jing Ma
AU - Yanan Yang
AU - Zhihao Shao
AU - Dandan Qin
AU - Xiaowei Chi
AU - Hongmei Xin
AU - Yue Jiang
AU - Haozheng Zhang
AU - Qinghua Liu
AU - Qin Dong
AU - Lijuan Zhang
AU - Kaihui Zhang
AU - Guohua Liu
PY - 2026
DA - 2026/11/04
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1977906
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1977906/full
AB - The X-linked ocular motor disorder known as FRMD7 associated infantile nystagmus syndrome: X-linked congenital nystagmus type 1 (NYS1; OMIM 310700) is typified by involuntary conjugate ocular oscillations starting in early infancy, typically without significant structural ocular abnormalities. Several infantile nystagmus waveforms are linked to pathogenic FRMD7 variants, which impair ocular motor development. A subset of affected individuals has been reported to exhibit periodic alternating nystagmus. In our clinical practice, we identified a male infant with nystagmus and conducted comprehensive testing on him and his parents. The proband exhibited persistent nystagmus at 1 months old and gradually worsened. Whole-exome sequencing revealed a novel intronic variant, c.206-9T>G in the FRMD7 gene (NM_194277.3) inherited from his unaffected mother. Pathogenicity analysis via minigene splicing assays demonstrated that the c.206-9T>G variant caused exon 4 (79 bp) skipping at the mRNA level. Based on the patient’s clinical features and functional validation of the genetic variant, the infant was diagnosed as X-linked congenital nystagmus type 1 (OMIM: 310700). The intronic variant c.206-9T>G happened in FRMD7 gene was verified pathogenic by minigene assay, and the study further broadened the mutational spectrum of FRMD7 and providing a molecular basis for genetic counseling for NYS1.
SN - 1664-2295
ER -