HPS1 GENE : ITS MUTATION AND FUNCTION

HPS1 基因：其突变和功能

• 批准号: 11670846
• 负责人: FUKAI Kazuyoshi
• 金额: $ 2.24万
• 依托单位: OSAKA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670846/
• 关键词: oculocutaneous albinism; mutation analysis; polymorphism; 多型

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.

我们能够在日本对6例Hermansky-Pudlak综合征患者进行突变分析。第一个病例是一个患有眼皮肤白化病的2岁女孩，分娩时出现肺出血。酪氨酸酶和P突变分析显示正常。她在突变热点的11号外显子有杂合移码突变。第二例为18岁男孩，有OCA和出血倾向。电镜下见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IVS 5 + 5 G>A纯合子，剪接位点突变。第4例为35岁男性，患有OCA和肾功能不全。他是IVS 1 - 9 C>T的纯合子，但通过研究50名正常对照，这被证明是非病理性的。第5例为70岁男性，OCA合并肺纤维化。他的HPS 1都正常。第6例为OCA合并肺纤维化，为IVS 5 + 5G>A剪接位点突变纯合子。对于那些我们无法检测到HPS 1基因突变的病例，我们正在与科罗拉多大学的Richard Spritz教授合作，他最近克隆了两个新的Hermansky-Pudlak综合征基因（HPS 3和HPS 4），看看这些病例是否属于这些新的类别。

项目成果

S. Saito, N. Oiso, T. Wada O Narazaki, K Fukai: "Angelman syndrome plus oculocataneous albinism type2 associated with a Pgene missence mutation"J Med Genet. (in press). (2000)

S. Saito、N. Oiso、T. Wada O Narazaki、K Fukai：“Angelman 综合征加眼白化病 2 型与 P 基因错失突变相关”J Med Genet。

KARichards,KFukai,Noiso AS Paller: "A novel KIT mutation results in piebaldism with progressive depigmentation"Journal of American Academy of Dermatology.. 44. 288-292 (2001)

KARichards、KFukai、Noiso AS Paller：“一种新型 KIT 突变导致花斑症并伴有进行性色素脱失”美国皮肤病学会杂志.. 44. 288-292 (2001)

S Saito,Noiso et al.: "Oculocutameous albinism type2 with a Pglue miscue mutation in a patient Augelar Tyalsome."Journal of Medical Genetics.. 37. 392-394 (2000)

S Saito, Noiso 等人：“患者 Augelar Tyalsome 中存在 Pglue 错误突变的 2 型眼皮肤白化病。”医学遗传学杂志.. 37. 392-394 (2000)

Saito S.et al.: "Oculocutaneous albinism type 2 with a P gene missense mutation in a patient with Angelman syndrome"J Med Genet. 37. 392-4 (2000)

Saito S.et al.：“Angelman 综合征患者伴有 P 基因错义突变的 2 型眼皮肤白化病”J Med Genet。

Horkawa T,Arakik,Fukaik et al.: "Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes"British Journal of Dermatology. 143. 635-640 (2000)

Horkawa T、Arakik、Fukaik 等人：“Hermansky-Pudlak 综合征伴有巨大黑素体的杂合 HPS1 突变”英国皮肤病学杂志。