Supplementary Material for: A Novel GUCY2D Frameshift Deletion Identified in a Patient with Leber Congenital Amaurosis 1: A Case Report

Introduction: This study aimed to describe the clinical characteristics of a 1-year-old male patient with Leber congenital amaurosis type 1 (LCA1) and investigate the genetic variations underlying his symptoms.

Case Presentation: A comprehensive medical history of the patient was obtained with thorough examinations via mydriatic optometry, fundus photography, and flash electroretinography. To identify causative mutations, whole-exome sequencing (WES) was conducted. Potential pathogenic mutations identified with WES were further validated via Sanger sequencing, which was also performed on family members to confirm the origins of the mutations. Based on clinical and laboratory findings, the patient was diagnosed with LCA1. Two heterozygous mutations in the GUCY2D gene, c.835G>A and c.2516_2517del, were detected in the patient with WES. Both mutations were assigned as likely pathogenic according to ACMG guidelines. c.2516_2517del has not been described previously. Sanger sequencing confirmed that the unaffected father and mother carried c.835G>A and c.2516_2517del, respectively.

Conclusion: The patient was a typical case of LCA1 with two GUCY2D mutations. To the best of our knowledge, this is the first report of the allele mutation c.2516_2517del in a patient with LCA1.

引言：本研究旨在描述1例1岁男性Leber先天性黑蒙1型（Leber congenital amaurosis type 1, LCA1）患者的临床特征，并探究其症状背后的遗传变异基础。
病例报告：我们收集了该患者完整的病史，并通过散瞳验光、眼底照相及闪光视网膜电图完成了全面检查。为明确致病突变，本研究进行了全外显子测序（whole-exome sequencing, WES）。通过WES筛选得到的潜在致病性突变，进一步通过桑格测序（Sanger sequencing）进行验证；同时对其家庭成员开展桑格测序，以确认突变的遗传来源。结合临床与实验室检查结果，该患者被确诊为LCA1。WES检测显示，该患者携带GUCY2D基因的两处杂合突变：c.835G>A与c.2516_2517del。根据美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics, ACMG）指南，上述两处突变均被判定为可能致病性突变。其中c.2516_2517del为此前未见报道的突变类型。桑格测序证实，表型正常的父母分别携带c.835G>A与c.2516_2517del突变。
结论：该患者为携带两处GUCY2D基因突变的典型LCA1病例。据我们所知，本研究为首次在LCA1患者中报道c.2516_2517del等位基因突变。