HPS1 GENE : ITS MUTATION AND FUNCTION

我们对日本的6例Hermansky-Pudlak综合征患者进行了突变分析。首例为1例2岁女童，患眼皮肤白化病，分娩时肺部出血。酪氨酸酶和P的突变分析显示正常。在突变热点的第11外显子有杂合性移码突变。第二例为18岁男孩，有OCA和出血倾向。他是IVS5+5G&gt；A和962-963 ins G的复合杂合子。在电子显微镜下，表皮黑素细胞内有巨大的黑素小体。第三例为49岁女性，患有OCA和肺纤维化。她是IVS5+5G&gt；A纯合子，剪接点突变。第四例为35岁男性，患有OCA和肾功能障碍。他是IVS1-9C&gt；T纯合子，但通过对50名正常对照组的研究发现，这是非病理的。第五例为70岁男性OCA合并肺纤维化。他对HPS1来说都是正常的。6例为OCA合并肺纤维化，为IVS5+5G&GT；A纯合子，剪接点突变。对于那些我们无法检测到HPS1基因突变的病例，我们正在与科罗拉多大学的理查德·斯普里茨教授合作，他最近克隆了两个新的赫曼斯基-普德拉克综合征基因(HPS3和HPS4)，看看这些病例是否属于这些新的类别。

We were able to perform mutation analysis of six cases with Hermansky-Pudlak syndrome in Japan. The first case was a 2-year-old girl with oculocutaneous albnism, and pulmonary hemorrhage when delivery. Mutation analysis of tyrosinase and P revealed normal. She has heterozygous frameshift muation in exon 11 in the mutation hotspot. The second case was 18-year-old boy with OCA and bleeding tendency. He was compound heterozygous for IVS5 +5 G>A and 962-963insG.Giant melanosomes were shown in the epidermal melanocytes by electronmicroscopy. The third case was 49-year-old woman with OCA and pulmonary fibrosis. She was homozygous for IVS5 +5 G>A, splice site mutation. The fourth case was 35-year-old man with OCA and renal dysfunction. He was homozygous for IVS1-9C>T, but this turned out to be non-pathological by studying 50 normal controls. The fifth case was 70-year-old man withOCA and pulmonary fibrosis. He was all normal for HPS1. The sixth case was OCA and pulmonary fibrosis, and was homozygous for IVS5 +5G>A, splice site mutation. For those in which we cannot detect mutations in HPS1 gene, we are collaborating with Professor Richard Spritz in the University of Colorado, who recently cloned two new Hermansky-Pudlak syndrome genes (HPS3 and HPS4), to see whether these cases might fall into these new categories.