Delas Flora, Koller Samuel, Maggi Jordi, Maspoli Alessandro, Kurmann Lisa, Lang Elena, Berger Wolfgang, Gerth-Kahlert Christina
Institute of Medical Molecular Genetics, University of Zurich, 8952 Schlieren, Switzerland.
Department of Ophthalmology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Int J Mol Sci. 2025 Jul 4;26(13):6454. doi: 10.3390/ijms26136454.
Peters anomaly (PA) is a rare congenital disorder within the anterior segment dysgenesis (ASD) spectrum, characterized by corneal opacity, iridocorneal adhesions, and potential systemic involvement. The genetic basis of PA and related syndromes are complex and incompletely understood. This study investigates novel genetic variants and their clinical impact in two unrelated individuals diagnosed with PA spectrum disorder. Whole-exome sequencing (WES), long-range PCR, and breakpoint analysis were applied to identify pathogenic variants. In the first patient, a heterozygous ~1.6 Mb deletion was detected, spanning the genes and (GRCh37 chr8:g.76760782_78342600del). The second patient carried a heterozygous variant (NM_001453.3:c.310A>G), classified as likely pathogenic. Both variants were confirmed by Sanger sequencing and considered de novo, as they were not present in the biological parents. Clinical evaluations revealed phenotypic variability, with the first patient displaying both ocular and systemic anomalies as in a Peters plus-like syndrome phenotype, while the second patient had isolated ocular manifestations as in a PA type 1 phenotype. These findings expand the genetic landscape of PA, underscoring the importance of comprehensive genomic analysis in subclassifying ASD disorders. Further studies are needed to elucidate the functional consequences of these variants and improve diagnostic and therapeutic strategies.
彼得斯异常（PA）是眼前节发育异常（ASD）谱系中的一种罕见先天性疾病，其特征为角膜混浊、虹膜角膜粘连以及可能的全身受累。PA及相关综合征的遗传基础复杂，尚未完全明确。本研究调查了两名被诊断为PA谱系障碍的无关个体中的新型遗传变异及其临床影响。应用全外显子组测序（WES）、长程PCR和断点分析来鉴定致病变异。在首例患者中，检测到一个杂合的约1.6 Mb缺失，跨越基因 和 （GRCh37 chr8:g.76760782_78342600del）。第二例患者携带一个杂合的 变异（NM_001453.3:c.310A>G），分类为可能致病。两个变异均通过桑格测序得到确认，并被认为是新生的，因为其生物学父母中不存在这些变异。临床评估显示出表型变异性，首例患者表现出眼部和全身异常，类似彼得斯附加样综合征表型，而第二例患者仅有孤立的眼部表现，类似PA 1型表型。这些发现扩展了PA的遗传图谱，强调了全面基因组分析在ASD疾病亚分类中的重要性。需要进一步研究以阐明这些变异的功能后果，并改进诊断和治疗策略。
