Department of Genetics, Institute of Ophthalmology "Conde de Valenciana", Chimalpopoca 14, Col. Obrera, Cuauhtemoc, CP 06800, Mexico City, Mexico.
Biochemistry Department, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
Graefes Arch Clin Exp Ophthalmol. 2023 Feb;261(2):353-365. doi: 10.1007/s00417-022-05786-4. Epub 2022 Aug 10.
To describe the results of clinical and molecular analyses in a group of patients suffering from inherited macular dystrophies, in which next-generation sequencing (NGS) efficiently detected rare causative mutations.
A total of eight unrelated Mexican subjects with a clinical and multimodal imaging diagnosis of macular dystrophy were included. Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field tests, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed by means of whole exome sequencing with subsequent Sanger sequencing validation of causal variants.
All patients exhibited a predominantly macular or cone-dominant disease. Patients' ages ranged from 12 to 60 years. Three cases had mutations in genes associated with autosomal dominant inheritance (UNC119 and PRPH2) while the remaining five cases had mutations in genes associated with autosomal recessive inheritance (CNGA3, POC1B, BEST1, CYP2U1, and PROM1). Of the total of 11 different pathogenic alleles identified, three were previously unreported disease-causing variants.
Macular dystrophies can be caused by defects in genes that are not routinely analyzed or not included in NGS gene panels. In this group of patients, whole exome sequencing efficiently detected rare genetic causes of hereditary maculopathies, and our findings contribute to expanding the current knowledge of the clinical and mutational spectrum associated with these disorders.
描述一组遗传性黄斑营养不良患者的临床和分子分析结果，其中下一代测序（NGS）有效地检测到罕见的致病突变。
共纳入 8 名无亲缘关系的墨西哥黄斑营养不良患者。视觉评估方法包括最佳矫正视力、眼底彩色照相、Goldmann 视野检查、动态视野检查、暗适应/明适应色觉视野检查、全视野视网膜电图、自发荧光成像和光谱域光学相干断层扫描成像。通过全外显子组测序进行基因筛查，随后对致病变异进行 Sanger 测序验证。
所有患者均表现为黄斑或锥细胞主导的疾病。患者年龄从 12 岁到 60 岁不等。3 例有常染色体显性遗传相关基因（UNC119 和 PRPH2）的突变，而其余 5 例有常染色体隐性遗传相关基因（CNGA3、POC1B、BEST1、CYP2U1 和 PROM1）的突变。在总共确定的 11 种不同的致病性等位基因中，有 3 种是以前未报道的致病变异。
黄斑营养不良可由常规分析或未包含在 NGS 基因面板中的基因缺陷引起。在这组患者中，全外显子组测序有效地检测到遗传性黄斑病变的罕见遗传原因，我们的发现有助于扩大对这些疾病相关临床和突变谱的认识。
