Paliwal Preeti, Gupta Jaya, Tandon Radhika, Sharma Namrata, Titiyal Jeewan S, Kashyap Seema, Sen Seema, Kaur Punit, Dube Divya, Sharma Arundhati, Vajpayee Rasik B
Laboratory of Cyto-Molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Mol Vis. 2010 Apr 28;16:729-39.
To study the clinical, histological, in vivo confocal microscopic, and molecular profile in a family with gelatinous drop-like corneal dystrophy (GDLD) from north India.
Two siblings from a consanguineous family presented with clinical features analogous to GDLD. Detailed clinical evaluations were performed for all the available affected and unaffected members of this family. In vivo confocal microscopy and histology was done wherever necessary. DNA isolated from peripheral blood samples was subjected to polymerase chain reaction (PCR) followed by direct sequencing to detect mutations in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. Protein modeling studies were done to asses the effect of the mutation on the protein structure.
The diagnosis of GDLD was established in the patient and the affected sibling on slit-lamp examinations, which revealed mulberry-like opacities in the subepithelium and anterior stroma that were confirmed on histopathology. The findings of the in vivo confocal microscopy were consistent with those reported in previous reports. Sequencing TACSTD2 revealed a novel homozygous missense mutation c.356G>A, leading to amino acid substitution C119Y in the two affected siblings. The mutation was found to be pathogenic on Sorting Intolerant From Tolerant (SIFT) analysis and was not found in normal controls and unaffected individuals of the family. A synonymous, previously reported, single nucleotide polymorphism (SNP; rs13267) was also seen in all the individuals of the family. Protein modeling studies involving wild-type and mutant protein indicated an exposed cysteine residue in the mutant protein.
A novel TACSTD2 C119Y mutation leading to an amino acid substitution was identified in two affected siblings of a family. Protein modeling studies revealed an exposed cysteine residue, which might cause interchain disulfide bond formation and protein aggregation leading to disturbed cell junctions of the corneal epithelium.
研究来自印度北部一个患有胶滴状角膜营养不良（GDLD）家庭的临床、组织学、活体共聚焦显微镜及分子特征。
一个近亲家庭的两名兄弟姐妹表现出与GDLD相似的临床特征。对该家庭所有可获得的患病和未患病成员进行了详细的临床评估。必要时进行了活体共聚焦显微镜检查和组织学检查。从外周血样本中提取的DNA进行聚合酶链反应（PCR），随后直接测序以检测肿瘤相关钙信号转导蛋白2（TACSTD2）基因中的突变。进行了蛋白质建模研究以评估该突变对蛋白质结构的影响。
通过裂隙灯检查在患者和患病的兄弟姐妹中确诊为GDLD，裂隙灯检查显示上皮下和前基质中有桑葚样混浊，组织病理学检查证实了这一点。活体共聚焦显微镜检查结果与先前报告一致。对TACSTD2进行测序发现两个患病兄弟姐妹中有一个新的纯合错义突变c.356G>A，导致氨基酸替换C119Y。该突变在耐受与不耐受排序（SIFT）分析中被发现具有致病性，在正常对照和该家庭的未患病个体中未发现。在该家庭的所有个体中还发现了一个先前报道的同义单核苷酸多态性（SNP；rs13267）。涉及野生型和突变型蛋白质的蛋白质建模研究表明突变型蛋白质中有一个暴露的半胱氨酸残基。
在一个家庭的两名患病兄弟姐妹中鉴定出一种导致氨基酸替换的新型TACSTD2 C119Y突变。蛋白质建模研究揭示了一个暴露的半胱氨酸残基，这可能导致链间二硫键形成和蛋白质聚集，从而导致角膜上皮细胞连接紊乱。
