King Richard A, Pietsch Jacy, Fryer James P, Savage Sarah, Brott Marcia J, Russell-Eggitt Isabelle, Summers C Gail, Oetting William S
Department of Medicine, University of Minnesota, Minneapolis, Minn. 55455, USA.
Hum Genet. 2003 Nov;113(6):502-13. doi: 10.1007/s00439-003-0998-1. Epub 2003 Sep 10.
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.
眼皮肤白化病（OCA）是一种常见的人类遗传病，由至少12种不同基因的突变引起。OCA1由酪氨酸酶基因突变所致，出生后表现为终生无黑色素（OCA1A），或出现少量至中等量的皮肤和眼部色素（OCA1B）。其他类型的OCA皮肤和眼部色素量各不相同。我们推测出生时头发白色提示OCA1，并在120例出生时头发白色的OCA先证者样本中进行了验证。我们发现，102例（85%）先证者患有OCA1，带有一或两个可识别的酪氨酸酶基因突变，204个OCA1酪氨酸酶基因等位基因中有169个（83%）有可识别的突变，35个（17%）在该基因的编码、剪接位点或近端启动子区域无可识别的变化。无法识别突变在OCA1B等位基因（24/35，69%）中比在OCA1A等位基因（11/35，31%）中更常见。7例无酪氨酸酶基因突变的先证者被发现患有OCA2，带有一或两个P基因突变，11例在这两个基因中均未检测到突变。我们得出结论：（1）出生时头发白色是一种有用的临床指标，提示患有OCA的儿童或成人可能为OCA1，尽管OCA2也可能有此表现；（2）酪氨酸酶和P基因的分子分析对于精确诊断是必要的；（3）存在酪氨酸酶基因无可识别突变的等位基因，特别是在OCA1B中，提示该基因更复杂的突变机制在OCA中很常见。
