施耐德角膜营养不良家系的UBIAD1基因突变分析

Mutation in the UBIAD1 gene of a Chinese family with Schnyder crystal corneal dystrophy

目的探讨施耐德角膜营养不良家系疾病的遗传学改变。方法对3例临床诊断为施耐德角膜营养不良患者、2名表型正常成员及健康人进行详细眼科检查，提取外周血DNA，根据UBIAD1基因的DNA序列设计引物，行PCR扩增，扩增产物直接测序，结果与Genebank数据库中UBIAD1基因所有外显子及其5’、3’非翻译区序列进行比对分析。结果该家系共调查4代15人，家系中其他患病者与先证者症状及临床表现类似，所有患者均见角膜周边老年环样脂质环，角膜中央区前基质层内有一环形、边缘不规则、类盘状黄白色细小针状结晶样混浊。共焦显微镜检查示角膜浅基质层内大量散在或成簇分布的方形、针状胆固醇结晶物。眼前节光学相干断层扫描显示前部基质高信号强度的致密物。所有临床确诊患者UBIAD1基因第一外显子均发现C．305A〉G改变，导致其编码的蛋白质第102位天冬酰胺（Asn）被丝氨酸（Ser）取代，其他家系成员及正常对照均无UBIAD1基因突变。结论UBIAD1基因错义突变C．305A〉G（P．Asnl02Ser）可能是导致该家系发病的原因；通过基因筛查可以协助临床医生明确诊断，并进行症状前诊断及产前诊断以防止疾病的发生。

Objective To investigate the genetic feature of Schnyder corneal dystrophy identified in a four-generation Chinese family. Method Ophthalmologic examinations were performed in 3 affected members and 2 unaffected members of a family with Sehnyder corneal dystrophy and controls. Genomic DNA was extracted from peripheral blood. The coding regions, 3＇UTR and 5＇UTR of UBIAD1 gene from all samples were screened by polymerase chain reaction （PCR） and direct DNA sequencing using the primers designed according to the sequence of UBIAD1, and comparatively analyzed with data from Genebank. Result The family has 15 members over 4 generations with similar signs and symptoms among proband and affected members. All affected members of the family demonstrated central discoid crystalline deposition with areus lipoides. Confocal microscopy examination showed multiple depositions of crystalline materials in anterior stroma. OCT showed the high reflective material localized within the anterior stroma. A missense mutation c. 305A 〉 G in 1 exon of UBIAD1 gene resulting in a substitution of Asparagine to Serine at codon 102（p. Asn102Ser） was found in all affected members of the family who were clinically diagnosed as Schnyder corneal dystrophy while not in the unaffected members of the family and controls. Conclusion The missense mutation c. 305A 〉 G （p. Asnl02Ser） of UBIAD1 gene may cause the disease of the family. Gene screen can assist clinicians in making definitive diagnosis, presymptomatic diagnosis and prenatal diagnosis.