ABSTRACT
Objective:To analyze the clinical phenotypes and pathogenic gene of a Han Chinese family with enhanced S-cone syndrome (ESCS).Methods:The method of pedigree investigation was adopted.A suspected ESCS Han Chinese family including 8 members of 3 generations was recruited in Henan Eye Hospital from June to September 2021.There was one patient in the family.A thorough ophthalmic examination of the proband was carried out to evaluate the phenotypes, including visual acuity, degree of strabismus, anterior segment and fundus, autofluorescence imaging, fluorescein fundus angiography, full-field electroretinogram (ERG), multifocal ERG, optical coherence tomography.DNA was extracted from peripheral blood samples from the proband and family members.The pathogenic gene and variation were screened by whole exome sequencing (WES).The variation and co-segregation were verified by Sanger sequencing.The deleteriousness of the variation was analyzed by SIFT, Polyphen2 and MutationTaster.The pathogenicity of the variation was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines.The analysis of amino acid sequence conservation was performed by SIFT.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2017[6]).Written informed consent was obtained from each subject.Results:This pedigree was consistent with autosomal recessive inheritance.The proband had clinical features such as night blindness, hyperopia, accommodative esotropia, peripheral retinal pigmentation, retinoschisis, and photopic ERG responses dominated by large-amplitude waves.Variations including a compound heterozygous variation, c.671C>T: p.S224L on exon 5 and c. 955G>A: p.E319K on exon 6 of NR2E3 were identified by WES.The variations were confirmed to be consistent with co-segregation.The both loci were missense variations, the variation frequency of which was 0 in the East Asian population via the gnomAD database.The variations were predicted to be deleterious by SIFT, Polyphen2 and MutationTaster.The c.671C>T variation was recorded with unknown significance in ClinVar database, and the c.955G>A variation was an unreported new locus.According to the ACMG Standards and Guidelines, the both variations were labeled as with uncertain clinical significance, and the corresponding amino acid sequences were highly conservative across multiple species. Conclusions:This family has the clinical characteristics of ESCS and meets the genetic diagnosis criteria.Two novel variations in NR2E3 gene, c.671C>T: p.S224L and 955G>A: p.E319K, are found.
ABSTRACT
Purpose: Enhanced S-cone syndrome (ESCS), a rare disorder, is often misdiagnosed as other forms of retinal degenerations, which have a poorer prognosis than ESCS. The aim of this study is to report the varied clinical features of ESCS and distinguish it from other similar disorders. Methods: We retrospectively scrutinized the records of patients with confirmed diagnosis of ESCS and analyzed the findings. Results: We included 14 patients (age range 4–39 years) who were confirmed to have ESCS according to pathognomonic electroretinography (ERG) showing reduced photopic, combined responses, and 30 Hz flicker with reduced L, M cone responses and supernormal S cone responses. The disease presented in the 1st decade with night blindness and was almost stationary or minimally progressive. Mid-peripheral fundus changes in form of nummular pigmentary alterations, yellow punctate lesions, and macular schisis were noted. The vision ranged from 6/6 to 6/36 with follow-up ranging from 1month to 22 years. Conclusion: ESCS shows varied clinical features ranging from unremarkable fundus to pigment clumping and atrophic lesions. It has good prognosis with patients mostly maintaining their vision. ERG is diagnostic. More awareness and knowledge about this entity can help to differentiate it from other forms of night blindness.