Molecular Analyses ofa Tyrosinase-negative AlbinoFamily
Molecular Analyses ofa Tyrosinase-negative AlbinoFamily
复制标题
酪氨酸酶阴性白化家族的分子分析
DOI：
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Sun‐Bang Kwon
中科院分区：
文献类型：
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作者：
Kyoung Chan Park;C. Chintamaneni;J. Witkop;Sun‐Bang Kwon
对一例酪氨酸酶阴性眼皮肤白化患者的酪氨酸酶编码区进行了简要序列分析，显示该患者为复合杂合子。1个等位基因在外显子3的第355位密码子上携带C-单碱基替换，另1个等位基因在外显子1内携带两个核苷酸缺失，核苷酸替换导致苏氨酸(ACA)到赖氨酸(AAA)的氨基酸突变，使N-糖基化信号消失。这对碱基对的缺失导致了一种移码，在第226位密码子上产生了一个推测的早熟终止信号。先证者和她的患病兄弟的单个核细胞是无性贫血的，没有可测量的酪氨酸酶活性。此外，免疫沉淀的前体和酪氨酸酶的凝胶电泳分析表明，该蛋白没有被加工成成熟的糖基化形式，证实了氨基酸变化的预测结果。同源等位基因的两个碱基缺失仅通过基因组DNA测序检测到，该等位基因的转录本在DNA文库中不存在，也不能被PCRmRNA检测到，免疫沉淀物中也不存在假定的截短蛋白(-25 kDa)，提示有正义突变的等位基因可能优先表达。
Summary Sequence analysis ofthetyrosinase coding region from an individual withtyrosinase-negative oculocutaneous albinism revealed that thepatient was a compound heterozygote. Oneallele carried a C--Asingle-base substitution incodon 355ofexon 3,andtheother carried atwo-nucleotide deletion inexon 1.Thenucleotide substitution caused aputative aminoacid change fromthreonine (ACA) tolysine (AAA), abolishing asignal for N-glycosylation. Thetwobase-pair deletion caused a frameshift, creating a putative prematuretermination signal atcodon 226.Themelanocytes fromtheproband andheraffected brother were amelanotic anddevoid ofmeasurable tyrosinase activity. Moreover, gelelectrophoretic analysis oftheimmunoprecipitated proband tyrosinase showed that theprotein was notprocessed tothe matureglycosylated form, confirming thepredicted consequenceoftheaminoacid change. Thetwo-base deletion on thehomologous allele was detected onlyby sequencing genomic DNA.Thetranscript ofthis allele was notrepresented inthecDNAlibrary andcould not bedetected byPCRmRNA,andtheputative truncated protein (-25kDa) was notpresentin immunoprecipitates, suggesting that theallele withthemissense mutation may bepreferentially expressed.
DOI：
10.1073/pnas.87.12.4809
发表时间：
1990-06-01
影响因子：
11.1
作者：
HALABAN, R;MOELLMANN, G
通讯作者：
MOELLMANN, G