Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Ophthalmic Genet. 2024 Feb;45(1):51-58. doi: 10.1080/13816810.2023.2196341. Epub 2023 Apr 5.
Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome with a wide range of phenotypic presentations, including characteristic facial features. A variety of ocular abnormalities have been described in patients with RSTS. The genetic etiology of RSTS is heterogeneous but often involves two major genes, CREBBP (cAMP-response element binding protein-binding protein) and EP300 (E1A binding protein p300), with CREBBP variants responsible for the majority of the cases.
We report a new case of female patient with a novel variant in CREBBP (c.4495C>G), with clinical features consistent with RSTS. We performed a literature review to search for possible genotype-phenotype relationships between the type of variant in CREBBP and frequency of ocular presentations. A PubMed search generated 12 articles that met our inclusion criteria. With the addition of our patient, there were a total of 163 patients included for mutation analysis (164 variants given one patient had two different variants).
Our review revealed that the most common variant types were frameshift (25%), gross deletion (23%), nonsense (18%), and intragenic deletions (13%). There does not appear to be an obvious hot spot location. A total of 127 patients were included for genotype-phenotype analysis of ocular features (36 patients were excluded as unable to discern variant type). The most frequent ocular features in patients with RSTS were down-slanting palpebral fissure (74%), arched eyebrows (56%), long eyelashes (52%), and strabismus (23%).
Our results suggest that currently there is no clear genotype-phenotype relationship between the type of variant and frequency of associated ocular features in RSTS patients.
Rubinstein-Taybi 综合征（RSTS）是一种罕见的遗传性综合征，具有广泛的表型表现，包括特征性的面部特征。RSTS 患者存在多种眼部异常。RSTS 的遗传病因具有异质性，但通常涉及两个主要基因，CREBBP（cAMP 反应元件结合蛋白结合蛋白）和 EP300（E1A 结合蛋白 p300），CREBBP 变体负责大多数病例。
我们报告了一例新的 CREBBP （c.4495C>G）新型变体的女性患者，其临床特征与 RSTS 一致。我们进行了文献回顾，以寻找 CREBBP 变异类型与眼部表现频率之间可能存在的基因型-表型关系。在 PubMed 上进行搜索，生成了 12 篇符合纳入标准的文章。加上我们的患者，共有 163 例患者进行了突变分析（164 个变异，因为有 1 例患者有两种不同的变异）。
我们的综述显示，最常见的变异类型是移码（25%）、大片段缺失（23%）、无义（18%）和内含子缺失（13%）。似乎没有明显的热点位置。共有 127 例患者纳入眼部特征的基因型-表型分析（36 例患者因无法识别变异类型而被排除）。RSTS 患者最常见的眼部特征是下斜睑裂（74%）、拱形眉毛（56%）、长睫毛（52%）和斜视（23%）。
我们的结果表明，目前在 RSTS 患者中，变异类型与相关眼部特征的频率之间没有明确的基因型-表型关系。
