ABSTRACT

Background

Most transforming growth factor beta-induced (TGFBI) corneal dystrophies are associated with a characteristic phenotype, clinical course, and a conserved mutation in the TGFBI gene. However, we report a novel TGFBI missense mutation associated with a late-onset, variant Bowman layer dystrophy.

Methods

Participants underwent slit-lamp examination and multimodal imaging. Polymerase chain reaction amplification and Sanger sequencing were performed on saliva-derived genomic DNA to screen TGFBI exons 4 and 12 as well as COL17A1 exon 46. PolyPhen-2 and SIFT were used to predict the functional impact of any identified variants.

Results

A 56-year-old Thai woman reported a four-year history of decreased vision and intermittent eye irritation, suggestive of recurrent epithelial erosions, in both eyes. Slit-lamp exam revealed bilateral, irregular, limbal-sparing Bowman layer opacities, which were also noted on anterior segment optical coherence tomography. Phototherapeutic keratectomy was performed in the right eye, improving the best-corrected visual acuity from 20/50 to 20/30. Sequencing of the TGFBI gene revealed a novel heterozygous, missense mutation in exon 12 (c.1571 C > G; p.Ser524Cys), which was present in an affected son and absent in an unaffected son, and was predicted to be damaging by PolyPhen-2 and SIFT. The patient was diagnosed with a variant Bowman layer dystrophy given the late onset of an atypical phenotype and the identification of a novel TGFBI mutation.

Conclusions

A novel TGFBI missense mutation is associated with a late-onset Bowman layer dystrophy. Given the atypical clinical appearance and course, molecular genetic analysis was utilized to establish a definitive diagnosis.

中文翻译：

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与迟发性复发性上皮糜烂和 Bowman 层混浊相关的新型 TGFBI 基因突变 (p.Serine524Cystine) 的鉴定。

摘要

背景

大多数转化生长因子 β 诱导的 ( TGFBI ) 角膜营养不良与特征性表型、临床病程和TGFBI基因的保守突变有关。然而，我们报告了一种新的TGFBI错义突变，该突变与迟发性变体 Bowman 层营养不良有关。

方法

参与者接受了裂隙灯检查和多模态成像。对唾液来源的基因组 DNA 进行聚合酶链反应扩增和 Sanger 测序，以筛选TGFBI外显子 4 和 12 以及COL17A1外显子 46。PolyPhen-2 和 SIFT 用于预测任何已识别变体的功能影响。

结果

一名 56 岁的泰国妇女报告了四年的视力下降和间歇性眼部刺激病史，提示双眼上皮糜烂复发。裂隙灯检查显示双侧、不规则、保留角膜缘的 Bowman 层混浊，这在眼前节光学相干断层扫描中也有发现。对右眼进行光疗性角膜切除术，将最佳矫正视力从 20/50 提高到 20/30。TGFBI的测序基因揭示了外显子 12 中的新杂合错义突变（c.1571 C > G；p.Ser524Cys），该突变存在于受影响的儿子中，而未受影响的儿子中不存在，并且预测 PolyPhen-2 和 SIFT 会造成损害. 考虑到非典型表型的迟发和新的TGFBI突变的鉴定，该患者被诊断为变异型 Bowman 层营养不良。

结论

一种新的TGFBI错义突变与迟发性 Bowman 层营养不良有关。鉴于非典型的临床表现和病程，分子遗传学分析被用来建立明确的诊断。