*Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom; †Department of Ophthalmology, St James's University Hospital, Leeds, United Kingdom; ‡Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico; §Department of Genetics, Institute of Ophthalmology "Conde de Valenciana," Mexico City, Mexico; and ¶Department of Ophthalmology, Bradford Royal Infirmary, Bradford, United Kingdom.
Cornea. 2014 Mar;33(3):247-51. doi: 10.1097/ICO.0000000000000041.
Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing loss. In addition, adult-onset Fuchs endothelial corneal dystrophy (FECD) is associated with dominant mutations in SLC4A11. In this report, we investigate whether patients with CHED go on to develop hearing loss and whether their parents, who are carriers of an SLC4A11 mutation, show signs of having FECD.
Patients with CHED were screened for mutations in the SLC4A11 gene and underwent audiometric testing. The patients and their parents underwent a clinical examination and specular microscopy.
Molecular analyses confirmed SLC4A11 mutations in 4 affected individuals from 3 families. All the patients were found to have varying degrees of sensorineural hearing loss at a higher frequency range. Guttate lesions were seen in 2 of the 4 parents who were available for examination.
Our observations suggest that CHED caused by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity of this may vary considerably. Patients with CHED should therefore be monitored for progressive hearing loss. We could not determine conclusively whether the parents of the patients with CHED were at increased risk of developing late-onset FECD.
SLC4A11 中的纯合突变可导致 2 种罕见的隐性疾病：单纯型先天性遗传性角膜营养不良（CHED），仅影响角膜；以及 Harboyan 综合征，由角膜营养不良和感觉神经性听力损失组成。此外，成人型 Fuchs 内皮角膜营养不良（FECD）与 SLC4A11 中的显性突变相关。在本报告中，我们研究了 CHED 患者是否会出现听力损失，以及携带 SLC4A11 突变的患者父母是否有 FECD 的迹象。
对 CHED 患者进行 SLC4A11 基因突变筛查，并进行听力测试。对患者及其父母进行临床检查和角膜共焦显微镜检查。
分子分析证实 3 个家系中的 4 名受影响个体存在 SLC4A11 突变。所有患者均发现高频范围存在不同程度的感觉神经性听力损失。有 2 名可供检查的父母存在点状病变。
我们的观察结果表明，由 SLC4A11 纯合突变引起的 CHED 进展为 Harboyan 综合征，但严重程度可能差异很大。因此，CHED 患者应监测进行性听力损失。我们无法确定 CHED 患者的父母是否有更高的风险患上迟发性 FECD。
