Authors:Li Jie, Li Zhanrong, Li Guanfeng, Jiang Yongqiang, Lu Xiaonan, Liu Xiaohui, Dai Shuzhen
Corresponding author:Dai Shuzhen, Email: dsz997300056@163.com
Published:2026-07-10
DOI: 10.3760/cma.j.cn115989-20251124-00403
ABSTRACT
Objective To analyze the clinical phenotypes and genetic characteristics of a Chinese Han pedigree with autosomal recessive enhanced S-cone syndrome (ESCS) caused by pathogenic variants in the Neural retina leucine zipper (NRL) gene, presenting with strabismus as the initial symptom.
Methods A pedigree investigation was conducted. A two-generation Chinese Han family with 5 members, including two ESCS patients, who first visited Henan Eye Hospital in July 2019, was enrolled. Detailed medical and family histories of the proband and family members were collected. All subjects underwent comprehensive ophthalmic examinations, including refraction, color vision test, strabismus angle measurement, ocular motility evaluation, fundus photography, Octopus static perimetry, optical coherence tomography (OCT), electroretinography (ERG), and visual evoked potential (VEP). Peripheral venous blood samples were collected from all family members for DNA extraction. Whole-exome sequencing (WES) was performed to screen candidate variants, followed by Sanger sequencing for verification of suspected variants, and pathogenicity of the identified variants was evaluated. This study complied with the Declaration of Helsinki, and the research protocol was approved by the Ethics Committee of Henan Eye Hospital (No. HNEECKY-2017[6]). Written informed consent was obtained from all participants and guardians of pediatric patients.
Results The proband was a 7-year-old girl presenting with intermittent exotropia combined with dissociated vertical deviation. Her younger sister presented with intermittent exotropia accompanied by compensatory head posture. They both exhibited latent nystagmus and mild visual impairment, with clustered pigmentary retinal degeneration. OCT revealed a disorganized neurosensory structure in the peripheral retina, while the macular area was relatively preserved. Static threshold perimetry revealed white-on-white field constriction (ring scotoma), while blue-on-yellow perimetry showed less constriction with markedly better sensitivity, suggesting enhanced S-cone function. ERG showed overall severely attenuated waveforms, with relatively preserved cone responses and essentially non-recordable rod responses. Whole-exome sequencing identified compound heterozygous variants in the NRL gene: c.434T>C (p.L145P) and c. 238C>T (p.Q80 *). The variant c. 434T>C was a novel variant. Sanger sequencing confirmed that these variants co-segregated with the disease phenotype within the pedigree. According to the American College of Medical Genetics and Genomics standards and guidelines for sequence variant interpretation, c.434T>C was classified as likely pathogenic, and c. 238C>T as pathogenic.
Conclusions A novel NRL variant c.434T>C is identified in this ESCS pedigree, and the patients are complicated with exotropia and compensatory head posture.
KEYWORDS：
Enhanced S-cone syndrome;Strabismus;NRL gene ;Autosomal recessive inheritance
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Authors Info & Affiliations
Li Jie
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
Li Zhanrong
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
Li Guanfeng
Department of Ophthalmology, Henan Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Henan Provincial Key Laboratory of Children’s Genetic and Metabolic Diseases, Zhengzhou 450018, China
Jiang Yongqiang
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
Lu Xiaonan
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
Liu Xiaohui
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
Dai Shuzhen
Department of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Henan Eye Hospital, Zhengzhou 450003, China
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