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Abstract：
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.
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.
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.
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.
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.
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.
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.
摘要：
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有关，临床课程，和TGFBI基因的保守突变.然而,我们报道了一个新的TGFBI错义突变，变异型Bowman层营养不良.
参与者接受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用于预测任何鉴定的变体的功能影响。
一名56岁的泰国妇女报告了四年的视力下降和间歇性眼睛刺激的病史，提示复发性上皮糜烂，在两只眼睛。裂隙灯检查显示双侧，不规则,保留角膜缘的鲍曼层混浊，在眼前段光学相干断层扫描中也注意到了这一点。在右眼进行了光疗角膜切除术，将最佳矫正视力从20/50提高到20/30。TGFBI基因的测序揭示了一个新的杂合，外显子12的错义突变（c.1571C>G;p.Ser524Cys），它存在于一个受影响的儿子身上，而不存在于一个未受影响的儿子身上，并预测会受到PolyPhen-2和SIFT的破坏。鉴于非典型表型的晚期发作和新的TGFBI突变的鉴定，该患者被诊断为变异型Bowman层营养不良。
一种新的TGFBI错义突变与迟发性Bowman层营养不良相关。鉴于非典型的临床表现和病程，分子遗传学分析用于建立明确的诊断。
参与者接受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用于预测任何鉴定的变体的功能影响。
一名56岁的泰国妇女报告了四年的视力下降和间歇性眼睛刺激的病史，提示复发性上皮糜烂，在两只眼睛。裂隙灯检查显示双侧，不规则,保留角膜缘的鲍曼层混浊，在眼前段光学相干断层扫描中也注意到了这一点。在右眼进行了光疗角膜切除术，将最佳矫正视力从20/50提高到20/30。TGFBI基因的测序揭示了一个新的杂合，外显子12的错义突变（c.1571C>G;p.Ser524Cys），它存在于一个受影响的儿子身上，而不存在于一个未受影响的儿子身上，并预测会受到PolyPhen-2和SIFT的破坏。鉴于非典型表型的晚期发作和新的TGFBI突变的鉴定，该患者被诊断为变异型Bowman层营养不良。
一种新的TGFBI错义突变与迟发性Bowman层营养不良相关。鉴于非典型的临床表现和病程，分子遗传学分析用于建立明确的诊断。
