Human Biochemical Genetics

人类生化遗传学部分研究了罕见的先天代谢错误，包括赫曼斯基？普德拉克综合征、胱氨酸病和尿碱性蛋白尿。1.该科成员继续在引起HPS的四个已知基因中发现突变，并寻找导致这种疾病的新基因。他们与其他科学家合作，帮助开发了一种检测血小板中5-羟色胺的方法，评估了一种用于患有血小板缺陷的人类的凝血分析仪，并描绘了患有肺纤维化的HPS患者的放射学特征。到目前为止，该科已检查、照顾和调查了120名HPS患者。2.该科成员跟踪调查了大约60名胱氨酸病患者，其中一些人在肾移植前，一些人在肾移植后。他们对新接触该方案的患者进行突变分析，积累治疗方案的纵向数据，并检测胱氨酸病的早期和晚期并发症。该科与国家眼科研究所的医生合作，利用吲哚青绿视频血管造影术，帮助描述了胱氨酸病的眼前段并发症和胱氨酸病的视网膜显影。该科还公布了半胱胺滴眼液新配方的研究报告。3.碱尿症是由于酪氨酸降解的中间产物--同质酸1，2-双加氧酶缺乏而导致的。症状包括从中年开始的关节和心脏瓣膜恶化。我们现在已经从临床、生化和分子基础上对60多名尿毒症患者进行了检查和调查。我们已经确定了我们患者中90%的导致尿蛋白尿的基因突变，并描述了一名患有尿蛋白尿和糖尿病肾病的男子，他的肾脏疾病加剧了他的时代病。两名患有尿酸尿症的妇女服用了小剂量的烟替酮，这是一种抑制产生高灵芝酸酶的药物。虽然血浆酪氨酸水平显著升高，但同种异构酸产量的降低为尼替松治疗碱尿症提供了原理证据。4.该科还研究各种罕见的人体新陈代谢疾病。该科成员已经确定了导致伊拉克裔犹太人和非伊拉克裔犹太人患者III型3-甲基谷氨酸尿症的基因和突变。他们描述了一名患有格里斯塞利综合征的患者，该患者的神经系统损害是由于rab27a基因的突变而不是预期的肌球蛋白5A基因造成的。在与其他研究人员的合作中，他们报告了由于编码溶酶体唾液酸转运体的基因突变而患上溶酶体游离唾液酸储存的患者。该科仍是世界？S诊断唾液酸代谢紊乱及其他游离唾液酸代谢紊乱的转诊实验室。

The Section on Human Biochemical Genetics investigates rare and informative inborn errors of metabolism, including Hermansky?Pudlak syndrome, cystinosis, and alkaptonuria. 1. Members of the Section continue to discover mutations in the four known genes causing HPS, and to search for new genes responsible for the disease. In collaboration with other scientists, they have helped develop an assay for detecting serotonin in platelets, evaluated a clotting analyzer for humans with platelet defects, and delineated the radiographic features of HPS patients with pulmonary fibrosis. The Section has examined, cared for,and investigated 120 HPS patients to date. 2. Members of the Section follow approximately 60 patients with cystinosis, some before and some after renal transplantation. They perform mutation analysis on patients new to the protocol, accumulate longitudinal data on treatment regimens, and detect early and late complications of cystinosis. In collaboration with physicians in the National Eye Institute, the Section has helped to describe anterior segment complications of cystinosis and retinal visualization in cystinosis using indocyanine green videoangiography. A study of a new formulation of cysteamine eyedrops was also promulgated by the Section. 3. Alkaptonuria results from accumulation of homogentisic acid, an intermediate in tyrosine degradation, due to deficiency of homogentisate 1,2-dioxygenase. The symptoms include joint and cardiac valve deterioration beginning in mid-life. We have now examined and investigated more than 60 alkaptonuria patients on clinical, biochemical, and molecular grounds. We have identified 90% of the genetic mutations causing alkaptonuria in our patients, and have described a man with alkaptonuria and diabetic nephropathy whose renal disease exacerbated his ochronosis. Two women with alkaptonuria were given low doses of nitisinone, a drug which inhibits the enzyme producing homogentisic acid. Although plasma tyrosine levels rose dramatically, the lowering of homogentisic acid production provides proof of principle for the use of nitisinone in alkaptonuria. 4. The Section also pursues a variety of other rare disorders of human metabolism. Members of the Section have identified the gene and the mutations responsible for type III 3-methylglutaconic aciduria in Iraqi-Jewish and non-Iraqi-Jewish patients. They have described a patient with Griscelli syndrome and neurological involvement caused by mutations in rab27a rather than the expected gene, myosin 5A. In collaboration with other investigators, they have reported patients with lysosomal free sialic acid storage due to mutations in the gene encoding the lysosomal sialic acid transporter. The Section remains the world?s referral laboratory for diagnosing sialuria and other disorders of free sialic acid metabolism.