Department of Genetics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Carrera de Médico Cirujano, Facultad De Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico.
Ophthalmic Genet. 2022 Apr;43(2):224-229. doi: 10.1080/13816810.2021.2002917. Epub 2021 Nov 29.
X-linked megalocornea (XMC) is a rare anterior segment malformation characterized by a nonprogressive enlargement of the cornea to 13 mm or greater in the setting of normal intraocular pressure. XMC is caused by mutations in the gene and it is inherited as an X-linked recessive trait affecting only males. Here, we describe the results of phenotypic and genetic assessment in a novel XMC pedigree.
Three subjects (a father and his two daughters) underwent a complete clinical and imaging ocular examination including biomicroscopy, fundoscopy, tonometry, visual acuity, Pentacam Scheimpflug imaging, anterior segment Swept Source OCT, and ultrabiomicroscopy. Genetic analysis was performed through whole exome sequencing in 3 family members. Candidate variants were validated by sanger sequencing.
The affected father exhibited megalocornea, very deep anterior chambers, retrocorneal pigmentation, iris atrophy, queer iris configuration, extremely open iridocorneal angles, and cataracts. Notably, both daughters showed queer iris configuration and abnormally widely open iridocorneal angles in both eyes. Genetic analysis identified a novel hemizygous c.207+1G>A splicing variant in in the affected father. Both mildly affected daughters were heterozygous for the pathogenic variant.
Here, we report an additional XMC family due to a novel mutation in the gene. Mild anterior segment anomalies were observed in two heterozygous carriers demonstrating for the first time a -linked phenotype in females. A detailed comparison of the clinical and genetic features of this pedigree with those observed in previously published XMC cases is also presented.
X 连锁型巨角膜症（XMC）是一种罕见的前部节段畸形，其特征为在正常眼压下角膜进行性扩大至 13mm 或更大。XMC 是由 基因突变引起的，作为 X 连锁隐性遗传性状，仅影响男性。在此，我们描述了一个新的 XMC 家系的表型和遗传评估结果。
3 位受试者（一位父亲及其两个女儿）接受了全面的临床和眼部影像学检查，包括生物显微镜检查、眼底检查、眼压测量、视力、Pentacam Scheimpflug 成像、前节 Swept Source OCT 和超生物显微镜检查。对 3 名家庭成员进行了全外显子组测序进行基因分析。候选变体通过 Sanger 测序进行验证。
受影响的父亲表现为巨角膜症、非常深的前房、角膜后色素沉着、虹膜萎缩、虹膜奇异形态、虹膜角膜角极宽、白内障。值得注意的是，两个女儿的双眼均表现出虹膜奇异形态和异常宽的虹膜角膜角。基因分析在受影响的父亲中发现了一个新的半合子 c.207+1G>A 剪接变异。两个轻度受影响的女儿均为该致病变异的杂合子。
在此，我们报告了一个新的 XMC 家系，该家系由 基因中的一个新突变引起。两个杂合子携带者出现了轻度的前节异常，这首次证明了女性存在 X 连锁表型。还对该家系与先前发表的 XMC 病例的临床和遗传特征进行了详细比较。
