HUMAN BIOCHEMICAL GENETICS

该科成员确定了导致良性（眼部）和中度胱氨酸病的CTNS突变，并回顾了世界上报道的CTNS突变。他们开发了一种多重PCR扩增方法，用于诊断在所检测的216个细胞分裂症等位基因中56%存在57kb缺失。该科继续用口服和局部（眼药水）半胱胺治疗100多名患者。2. 在与NHGRI研究人员的合作下，发现了一个与CTNS相邻的新基因。这个被称为CARKL的基因可能产生一种碳水化合物激酶，并可能区分患有57 kb缺失的胱氨酸病患者和非缺失患者。它有一个1434 bp的开放阅读框，7个外显子编码一个478个氨基酸的蛋白。3.9 kb的转录本在肝脏、肾脏和胰腺中显著表达。3. 世界上第5例唾液尿症患者已被确诊。这名7岁的葡萄牙女孩携带一份含有R266Q突变的UDP-GlcNAc 2- epimase基因拷贝，100微摩尔cmp -唾液酸对该酶的抑制作用仅为26%（正常为79%）。4. 超过95名患有Hermansky Pudlak综合征（HPS）的患者现在已经在NIH临床中心进行了检查，并描述了该疾病的肺部，皮肤和眼科方面的情况。该科成员还鉴定并临床鉴定了两名HPS患者，他们是AP-3 β - 3a亚基突变的复合杂合子，AP-3是一种负责囊泡运输和货物分拣的接头蛋白复合物。-胱氨酸病，唾液尿，Hermansky-Pudlak综合征，囊泡贩运，突变分析-人类受试者

Members of the Section have determined the CTNS mutations responsible for benign (ocular) and intermediate cystinosis, and have reviewed the worlds reported CTNS mutations. They have developed a multiplex PCR amplification method for diagnosing the presence of the 57-kb deletion present in 56% of 216 cytinosis alleles tested. The Section continues to treat over 100 patients with oral and topical (eyedrop) cysteamine. 2. In collaboration with NHGRI investigators, a new gene adjacent to CTNS was discovered. The gene, called CARKL, presumably produces a carbohydrate kinase and may distinguish cystinosis patients bearing the 57-kb deletion from nondeletion patients. It has a 1434 bp open reading frame with 7 exons encoding a 478 amino acid protein. Expression of a 3.9 kb transcript occurs prominently in liver, kidney, and pancreas. 3. The fifth patient in the world with sialuria has been characterized. This 7-year old Portuguese girl carries a single copy of a UDP-GlcNAc 2-epimerase gene containing an R266Q mutation, and the resulting enzyme is inhibited only 26% by 100 micromolar CMP-sialic acid (normal, 79%). 4. More than 95 patients with Hermansky Pudlak syndrome (HPS) have now been examined at the NIH Clinical Center, and the pulmonary, dermatologic, and ophthalmologic aspects of the disorder have been described. Members of the Section have also identified and clinically characterized two HPS patients who are compound heterozygotes for mutations in the beta-3A subunit of AP-3, an adaptor protein complex responsible for vesicular trafficking and cargo sorting. - Cystinosis, sialuria, Hermansky-Pudlak syndrome, vesicular trafficking, mutation analysis - Human Subjects