Department of Ophthalmology, Shamir Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Private Practice, Ramla, Israel.
Exp Eye Res. 2020 Nov;200:108220. doi: 10.1016/j.exer.2020.108220. Epub 2020 Sep 6.
Our study describes the glaucoma phenotype in a family with Axenfeld-Rieger syndrome (ARS) and a FOXC1 variant. Included were 20 subjects from a large three generation family of Jewish Indian ancestry. Subjects underwent a comprehensive ophthalmic examination including automated perimetry and optical coherence tomography. Eight subjects were available for molecular analysis which included whole genome sequencing on selected patients and Sanger sequencing for variant screening. Eleven patients demonstrated a wide spectrum of Axenfeld-Rieger anomaly signs and symptoms. These ranged from subtle angle abnormalities to remarkable anterior segment abnormalities such as corectopia, iris adhesions and strands. Among them, six had glaucoma and two were glaucoma suspects. Of the six subjects with glaucoma three had high-tension glaucoma and two had normal-tension glaucoma. Molecular analysis revealed a previously described pathogenic variant in the FOXC1 gene (c.378C > G p.I126M; rs104893958), in six affected patients which was not identified in two healthy siblings. Molecular analysis also revealed a PITX2 missense variant (c.28T > A p.L10M; rs755864040) which did not segregate with clinical findings and was considered likely benign. In conclusion, patients with ARS due to FOXC1 variants may present with glaucomatous optic nerve damage without apparent elevation in IOP. Normal-tension glaucoma is less commonly reported in individuals with ARS and a comprehensive glaucoma assessment may be warranted in these individuals even with normal IOP. These findings raise the possibility that glaucomatous damage associated with FOXC1 is not only due to high IOP.
我们的研究描述了一个具有 Axenfeld-Rieger 综合征（ARS）和 FOXC1 变体的家族的青光眼表型。研究对象包括一个具有犹太印度血统的三代大家庭中的 20 名受试者。受试者接受了全面的眼科检查，包括自动视野检查和光学相干断层扫描。有 8 名受试者可进行分子分析，包括对选定患者进行全基因组测序和对变体进行 Sanger 测序筛选。11 名患者表现出广泛的 Axenfeld-Rieger 异常体征和症状。这些症状从轻微的角度异常到显著的前节异常，如核心异位、虹膜粘连和条索。其中，6 人患有青光眼，2 人是青光眼疑似患者。在 6 名患有青光眼的患者中，有 3 人患有高血压性青光眼，2 人患有正常眼压性青光眼。分子分析显示，FOXC1 基因（c.378C > G p.I126M；rs104893958）中的一个先前描述的致病性变体存在于 6 名受影响的患者中，但在 2 名健康的兄弟姐妹中未发现。分子分析还显示了 PITX2 错义变体（c.28T > A p.L10M；rs755864040），该变体与临床发现不一致，被认为可能是良性的。总之，由于 FOXC1 变异引起的 ARS 患者可能表现为没有明显眼压升高的青光眼视神经损伤。正常眼压性青光眼在 ARS 患者中较少见，即使眼压正常，这些患者也可能需要进行全面的青光眼评估。这些发现提出了这样一种可能性，即与 FOXC1 相关的青光眼损伤不仅是由于高眼压引起的。
