【摘要】 目的 对5例眼皮肤白化病（OCA）患者进行基因诊断及遗传咨询。方法 收集患者的临床表型并抽取患者及父母外周血，进行全外显子组测序，基因突变位点根据美国医学遗传学与基因组学学会（ACMG）变异指南进行判读，对未报道过的新位点进行分析。结果 全外显子组测序结果显示病例1:TYR c.1181A>G(p.D394G)（纯合突变）；病例2:TYR c.929dupC(p.R311K fs~*7)（父源）与c.709G>A(p.D237N)（母源）复合杂合突变；病例3:TYR c.896G>A(p.R299H)（父源）与c.593T>G(p.I198S)（母源）复合杂合突变；病例4:TYR c.1199G>T(p.W400L)（纯合突变）；病例5:TYRP1 c.1057＿1060del(p.N353Vfs~*31)（父源）与c.1409-2A>T（母源）复合杂合突变。通过临床表型和基因检测对5例白化病患者进行确诊并分型。结论 由于OCA的临床表现有明显的重叠，单纯根据临床表型难以分型，分子检测有助于对OCA患者准确诊断和分类。另外，本研究首次发现TYR基因2个新突变位点，分别为c.1181A>G(p.D394G)、c.709G>A(p.D237N),TYRP1基因1个新突变位点c.1409-2A>T。新基因突变位点的发现完善了眼皮肤白化病的基因型与表型谱，并为患者及父母的再次生育提供指导意见。更多还原

【Abstract】 Objective Genetic diagnosis and genetic counseling were performed for five patients with oculocutaneous albinism. Methods The study collected clinical phenotypes of patients and extracted genomic DNA from peripheral blood samples of proband and their parents. The DNA of the proband was sequenced by whole exome and the mutation site was verified by parents. The mutation sites were interpreted according to the variation guidelines of ACMG, and the pathogenicity of the unreported new sites was analyzed. Results The results of the whole exome sequencing indicate the following mutations:Case 1: TYR c.1181A>G p.D394G(homozygous mutation); Case 2: TYR c.929dupC p.R311K fs~*7(paternal) and c.709G>A p.D237N(maternal) compound heterozygous mutation; Case 3: TYR c.896G>A p.R299H(paternal) and c.593T>G p.I198S(maternal) compound heterozygous mutation; Case 4: TYR c.1199G>T p.W400L(homozygous mutation); Case 5: TYRP1c.1057＿1060del p.N353Vfs~*31(paternal) and c.1409-2A>T(maternal) compound heterozygous mutation. Five patients with albinism were diagnosed and typed by clinical phenotype and gene mutation. Conclusion Molecular testing is crucial for accurately diagnosing and classifying patients with OCA due to the significant overlap in clinical manifestations. Our study identified two previously unknown mutation sites in the TYR gene, specifically c.1181A>G p.D394G and c.709G>A p.D237N,as well as a new mutation site in the TYRP1 gene, c.1409-2A>T. The discovery of new gene mutation loci has expanded the genotypic and phenotypic spectrum of oculocutaneous albinism. This provides guidance for patients and their parents regarding reproduction.更多还原