Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype
Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype
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DOI：
10.1007/s00439-003-0998-1
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发表时间：
2003-11-01
期刊：
影响因子：
5.3
通讯作者：
Oetting, WS
中科院分区：
文献类型：
--
作者：
King, RA;Pietsch, J;Oetting, WS
眼皮肤白化病（OCA）是一种常见的人类遗传疾病，至少由12种不同基因的突变引起。OCA 1由酪氨酸酶基因突变引起，出生后终生缺乏黑色素（OCA 1A）或出现极少量至中等量的皮肤和眼部色素（OCA 1B）。其他类型的OCA有不同数量的皮肤和眼睛色素。我们假设出生时有白色头发表示OCA 1，并在120名出生时有白色头发的OCA先证者样本中进行了测试。我们发现，102（85%）的先证者有一个或两个可识别的酪氨酸酶基因突变的OCA 1，与169（83%）的204 OCA 1酪氨酸酶基因等位基因具有可识别的突变和35（17%）没有可识别的变化，在编码，剪接连接，或近端启动子区的基因。OCA 1B等位基因（24/35，69%）无法识别突变比OCA 1A等位基因（11/35，31%）更常见。7名先证者没有酪氨酸酶基因突变，发现有一个或两个P基因突变的OCA 2，在11个，没有检测到任何基因突变。我们得出的结论是：（1）出生时存在白色头发是一个有用的临床工具，表明患有OCA的儿童或成人患有OCA 1，尽管OCA 2也可能具有这种表现;（2）对酪氨酸酶和P基因的分子分析对于精确诊断是必要的;和（3）存在酪氨酸酶基因没有可识别突变的等位基因，特别是在OCA 1B中，表明该基因更复杂的突变机制在OCA中很常见。
Oculocutaneous albinism (OCA) is a common human genetic condition resulting from mutations in at least twelve different genes. OCA1 results from mutations of the tyrosinase gene and presents with the life-long absence of melanin pigment after birth (OCA1A) or with the development of minimal-to-moderate amounts of cutaneous and ocular pigment (OCA1B). Other types of OCA have variable amounts of cutaneous and ocular pigment. We hypothesized that white hair at birth indicates OCA1 and tested this in a sample of 120 probands with OCA and white hair at birth. We found that 102 (85%) of the probands had OCA1 with one or two identifiable tyrosinase gene mutations, with 169 (83%) of the 204 OCA1 tyrosinase gene alleles having identifiable mutations and 35 (17%) having no identifiable change in the coding, splice junction, or proximal promoter regions of the gene. The inability to identify the mutation was more common with OCA1B (24/35, 69%) than with OCA1A (11/35, 31%) alleles. Seven probands with no tyrosinase gene mutations were found to have OCA2 with one or two P gene mutations, and in eleven, no mutations were detected in either gene. We conclude that (1) the presence of white hair at birth is a useful clinical tool suggesting OCA1 in a child or adult with OCA, although OCA2 may also have this presentation; (2) the molecular analysis of the tyrosinase and P genes are necessary for precise diagnosis; and (3) the presence of alleles without identifiable mutations of the tyrosinase gene, particularly in OCA1B, suggests that more complex mutation mechanisms of this gene are common in OCA.