Shuhan Si, Xueyuan Jia, Lidan Xu, Qian Qin, Jie Wu, Wei Ji, Kexian Dong, Xuelong Zhang, Lin Cao, Hao Wang, Peng Liu, Rongrong Wang, Jing Bai, Songbin Fu, Yun Huang, Wenjing Sun
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Functional prediction of variants was performed by various bioinformatic analyses, while the pathogenicity classification of variants was evaluated according to ACMG standards and guidelines. A missense variant NM_000372.5:c.107G > C;NP_000363.1:p.C36S was discovered in <i>TYR</i> gene which converted cysteine to serine. Another variant in intron, NM_000372.5:c.1037–7 T > A, also affected the function of <i>TYR</i> gene. We verified the pathogenicity of the intron variant with a pCAS2 mini-gene based splicing assay and found that c.1037–7 T > A led to an insertion of 5 bp upstream from the common acceptor site of exon 3, which caused a frameshift <i>TYR</i>:c.1037–7 T > A:p.G346Efs*11. The results showed that the compound heterozygous variants c.107G > C:p.C36S and c.1037–7 T > A:p.G346Efs*11 of <i>TYR</i> gene were the pathogenic variants for this OCA1 family.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"472-480"},"PeriodicalIF":3.9000,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and characterization of the compound heterozygous variants of TYR gene in a northern Chinese family with Oculocutaneous albinism type 1\",\"authors\":\"Shuhan Si, Xueyuan Jia, Lidan Xu, Qian Qin, Jie Wu, Wei Ji, Kexian Dong, Xuelong Zhang, Lin Cao, Hao Wang, Peng Liu, Rongrong Wang, Jing Bai, Songbin Fu, Yun Huang, Wenjing Sun\",\"doi\":\"10.1111/pcmr.13111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Oculocutaneous albinism (OCA) is a genetically heterogeneous disease and is most inherited in an autosomal recessive manner. 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引用次数: 0
摘要
眼部皮肤白化病(OCA)是一种遗传异质性疾病,大多数以常染色体隐性遗传方式遗传。OCA的特征性表现是由于黑色素合成功能紊乱。OCA1是OCA最严重的亚型,由酪氨酸酶(TYR)基因的纯合或复合杂合变体引起,酪氨酸酶是黑色素合成的关键基因。本研究旨在鉴定中国北方一个OCA1家族的遗传变异。收集临床资料和外周血样本。采用PCR扩增和Sanger测序方法检测TYR基因的全部外显子和相邻侧翼序列。通过各种生物信息学分析进行变异的功能预测,同时根据ACMG标准和指南评估变异的致病性分类。错义变体NM_000372.5:c.107G > CNP_000363.1:p.C36S是在TYR基因中发现的,该基因将半胱氨酸转化为丝氨酸。内含子中的另一个变体,NM_000372.5:c.1037-7 T > A、 也影响TYR基因的功能。我们用pCAS2小基因剪接试验验证了内含子变体的致病性,发现c.1037-7 T > A导致插入5 外显子3的共同受体位点上游的bp,其引起TYR:c.1037-7的移码 T > A: p.G346Efs*11.结果表明,复合杂合变异体c.107G > C: p.C36S和C.1037-7 T > A: TYR基因的p.G346Efs*11是该OCA1家族的致病性变体。
Identification and characterization of the compound heterozygous variants of TYR gene in a northern Chinese family with Oculocutaneous albinism type 1
Oculocutaneous albinism (OCA) is a genetically heterogeneous disease and is most inherited in an autosomal recessive manner. The characteristic manifestation of OCA is due to disfunction of melanin synthesis. OCA1 is the most severe subtype of OCA and is caused by homozygous or compound heterozygous variants in tyrosinase (TYR) gene, which is the key gene for melanin synthesis. This study aimed to identify the genetic variants of a northern Chinese family with OCA1. Clinical information and peripheral blood samples were collected. PCR amplification and Sanger sequencing were used to detect the entire exons and adjacent flanking sequences of TYR gene. Functional prediction of variants was performed by various bioinformatic analyses, while the pathogenicity classification of variants was evaluated according to ACMG standards and guidelines. A missense variant NM_000372.5:c.107G > C;NP_000363.1:p.C36S was discovered in TYR gene which converted cysteine to serine. Another variant in intron, NM_000372.5:c.1037–7 T > A, also affected the function of TYR gene. We verified the pathogenicity of the intron variant with a pCAS2 mini-gene based splicing assay and found that c.1037–7 T > A led to an insertion of 5 bp upstream from the common acceptor site of exon 3, which caused a frameshift TYR:c.1037–7 T > A:p.G346Efs*11. The results showed that the compound heterozygous variants c.107G > C:p.C36S and c.1037–7 T > A:p.G346Efs*11 of TYR gene were the pathogenic variants for this OCA1 family.
期刊介绍:
Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords
Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders