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目的:分析1个眼皮肤白化病(oculocutaneous albinism，OCA)患者家系的基因变异情况。方法:采用芯片捕获高通量测序与Sanger测序技术对先证者及其父母进行基因测序，应用PolyPhen-2、SIFT、MutationTaster和FATHMM软件对新变异进行功能预测，同时对该家系的4例白化病患者进行系谱和变异基因分析。结果:测序结果显示先证者n TYR基因(NM_000372)存在c.230G>A(p.Arg77Gln)和c.120_121insG(p.Asp42GlyfsTer35)复合杂合变异，先证者父亲携带c.230G>A杂合变异，母亲携带c.120_121insG杂合变异，表明先证者的2个变异分别来自父亲和母亲。前者属于已知的错义变异，该变异可导致蛋白质多肽链原有功能的异常或丧失。后者c.120_121insG(p.Asp42GlyfsTer35)为未报道过的n TYR基因亚区(EX1；CDS1)的移码变异。应用PolyPhen-2、SIFT、MutationTaster和FATHMM预测，均提示为“有害变异”。该变异导致氨基酸编码蛋白发生提前终止，产生截短蛋白，最终形成76个氨基酸的短型TYR蛋白。通过家系分析，该家系4例患者均为同类型复合杂合变异，致病基因均来自患者父母，属于5代以内的特殊形式近亲婚配。n 结论:TYR基因c.230G>A(p.Arg77Gln)和c.120_121insG(p.Asp42GlyfsTer35)复合杂合变异可能为该家系患者的致病原因，新变异的检出丰富了n TYR基因的变异谱，可以为家系的遗传咨询和产前诊断提供理论依据。n “,”Objective:To analyze gene variants in a Chinese pedigree with oculocutaneous albinism (OCA).Methods:Gene sequencing of the proband and his parents was performed using chip capture high-throughput sequencing and Sanger sequencing techniques, and PolyPhen-2, SIFT, MutationTaster, and FATHMM software were used to predict the function of new variants.At the same time, the pedigree and variant genes of 4 albinism patients from this pedigree were analyzed.Results:Sequencing results showed that the proband’s n TYR gene (NM_000372) has c. 230G>A (p.Arg77Gln) and c. 120_121insG (p.Asp42GlyfsTer35) compound heterozygous variants.The proband’s father carries c. 230G>A heterozygous variant, and the mother carries c. 120_121insG heterozygous variant, indicating that the proband’s two variants are from his father and mother.The former is a known missense variant, which can cause abnormal or loss of the original function of the protein polypeptide chain.The latter c. 120_121insG (p.Asp42GlyfsTer35) is an unreported frameshift variant of then TYR gene subregion (EX1; CDS1). PolyPhen-2, SIFT, MutationTaster and FATHMM predictions are all prompted as “harmful variants” . This variant caused the amino acid-encoded protein to terminate prematurely, producing a truncated protein, which eventually formed a 76-amino acid short-type TYR protein instead of the 529-amino acid wild-type TYR protein.Through the pedigree analysis, the four patients in the pedigree are all of the same type of compound heterozygous variants, and the disease-causing genes are all from the patient’s parents. They belong to a special form of consanguineous marriage within 5 generations.n Conclusion:The compound heterozygous variants of c. 230G>A (p.Arg77Gln) and c. 120_121insG (p.Asp42GlyfsTer35) of then TYR gene may underlie the disease in this pedigree.The gene sequencing results enrich the variant spectrum of the n TYR gene, and has facilitated molecular diagnosis for the patient.n