Chacon-Camacho Oscar F, Ordaz-Robles Thania, Cid-García Marion A, Yepes-Rodríguez Olivia, Arce-González Rocio, Martínez-Aguilar Alan, Zenteno Juan Carlos
Department of Genetics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Laboratorio 5 Edificio A-4, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de, Mexico City, Mexico.
Am J Med Genet A. 2025 Jan;197(1):e63869. doi: 10.1002/ajmg.a.63869. Epub 2024 Sep 12.
Doyne honeycomb retinal dystrophy (DHRD), also termed malattia leventinese (MLVT), is a dominantly inherited ocular disease characterized by the progressive accumulation of macular and peripapillary drusenoid material beneath the retinal pigment epithelium in the Bruch membrane. In all affected individuals genetically characterized to date, DHRD/MLVT is caused by a single heterozygous p.Arg345Trp missense variant in the EGF-containing fibulin-like extracellular matrix protein 1, EFEMP1. Recently, pathogenic variants in the EFEMP1 gene have also been demonstrated in several families with juvenile or adult-onset hereditary isolated glaucoma. Here, we describe a family featuring a unique phenotype of juvenile glaucoma and DHRD/MLVT caused by a novel EFEMP1 variant. Our results expand both the ocular phenotype associated with EFEMP1 variants and the molecular spectrum causing DHRD by describing the first non-p.Arg345Trp EFEMP1 pathogenic allele.
多伊内蜂窝状视网膜营养不良（DHRD），也称为莱文廷病（MLVT），是一种常染色体显性遗传性眼病，其特征是视网膜色素上皮下布鲁赫膜中黄斑和视乳头周围类玻璃膜疣物质逐渐积累。在迄今所有已进行基因特征分析的受影响个体中，DHRD/MLVT是由含表皮生长因子的纤维连接蛋白样细胞外基质蛋白1（EFEMP1）中的单个杂合p.Arg345Trp错义变异引起的。最近，在几个患有青少年或成人型遗传性单纯性青光眼的家族中也发现了EFEMP1基因的致病变异。在此，我们描述了一个家族，其具有由一种新型EFEMP1变异导致的青少年青光眼和DHRD/MLVT的独特表型。我们的研究结果通过描述首个非p.Arg345Trp的EFEMP1致病等位基因，扩展了与EFEMP1变异相关的眼部表型以及导致DHRD的分子谱。
