Human Biochemical Genetics

人类生化遗传学

• 批准号: 6829337
• 负责人: William Allen Gahl
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6829337
• 关键词: albinism; cell components; cytogenetics; enzyme deficiency; gene expression; gene mutation; genetic disorder; human genetic material tag; human subject; inborn aminoacid metabolism disorder; molecular genetics; orphan disease /drug; phenylacetates; platelet disorder; polycystic kidney; tissue /cell culture; albinism; cell components; cytogenetics; enzyme deficiency; gene expression; gene mutation; genetic disorder; human genetic material tag; human subject; inborn aminoacid metabolism disorder; molecular genetics; orphan disease /drug; phenylacetates; platelet disorder; polycystic kidney; tissue /cell culture

The Section on Human Biochemical Genetics studies selected inborn errors of metabolism to provide insight into cellular mechanisms and care for abandoned populations of patients. 1. Hermansky-Pudlak syndrome (HPS) is a rare disorder of oculocutaneous albinism and bleeding due to abnormal formation of melanosomes and platelet dense bodies. There are 7 genetic subtypes of this disease. Members of the Section described 6 new, non-Puerto Rican HPS-1 patients along with 4 novel HPS1 mutations, and 7 new, non-Puerto Rican HPS-4 patients having 3 novel HPS4 mutations. We continue to define the natural history of clinical involvement in the subtypes of HPS, and to perform cell biological studies of the movement of intracellular vesicles in these disorders. 2. This year members of the Section admitted more than 70 cystinosis patients to the Clinical Center, following their treatment with cysteamine and documenting the presence or absence of nonrenal complications of the disorder. One 25-year old man had coronary artery disease, and this is now being reported as a late complication of cystinosis. One woman carrying the diagnosis of ocular cystinosis was diagnosed instead with multiple myeloma. Two siblings treated well with cysteamine were reported to have excellent kidney function and growth at ages 14 and 8. In collaboration with the National Eye Institute, members of the Section continue to investigate cysteamine eyedrops for the treatment of corneal cystine crystals. 3. The Section has expanded its expertise in alkaptonuria, a disorder of accumulation of homogentisic acid due to deficiency of homogentisate 1,2-dioxygenase. The Section documented the natural history of the disease with respect to joints, kidney stones, and cardiac valves, and began therapy in 5 patients with nitisinone, which reduced the toxic homogentisic acid by 95%. Mutation analysis was also performed in patients enrolled in the Section?s studies. 4. Members of the Section diagnosed and described three different patients with disorders of free sialic acid metabolism, i.e., Salla disease and Infantile Free Sialic Acid Storage Disease. These disorders results from defective sialin, the lysosomal membrane transport protein which carries free sialic acid out of lysosomes. 5. The Section also studied selected rare disease patients, including two with Gray Platelet Syndrome and three with Hereditary Inclusion Body Myopathy. The deficient enzyme in this latter disease, UDP-GlcNAc 2-epimerase, was assayed in cultured fibroblasts. Mutation analysis was also performed on the patients? DNA. Protocols were initiated to find the gene causing Gray Platelet Syndrome and to document the natural history of Autosomal Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis.

人类生物化学遗传学研究部分选择了代谢的先天错误，以洞悉细胞机制，并照顾被废弃的患者人群。 1。Hermansky-Pudlak综合征（HPS）是一种罕见的眼皮白化病和由于异常形成黑素体和血小板致密体而出血的罕见疾病。该疾病有7种遗传亚型。本节的成员描述了6名新的，非Puerto Rican HPS-1患者以及4种新型的HPS1突变，还有7例具有3种新型HPS4突变的新的，非Puerto Rican HPS-4患者。我们继续定义临床参与HPS亚型的自然史，并对这些疾病中细胞内囊泡运动进行细胞生物学研究。 2。本节的成员在用cysteamine治疗并记录了该疾病的存在或不存在后，将70多名囊肿患者送往临床中心。一名25岁的男子患有冠状动脉疾病，现在据报道是囊肿性的晚期并发症。诊断为多发性骨髓瘤，诊断出一名携带眼囊肿病诊断的妇女。据报道，用cysteamine良好治疗的两个兄弟姐妹在14和8岁时具有出色的肾功能和生长。与国家眼科研究所合作，该部分的成员继续研究Cysteamine EyeDrops，以治疗角膜胱氨酸晶体。 3。该部分扩大了其在烷烃的专业知识，这是由于均匀剂量1,2-二氧酶的缺乏而导致均匀酸的积累障碍。该部分记录了该疾病的自然史，相对于关节，肾结石和心脏瓣膜，并开始对5例硝酸酮患者进行治疗，从而使毒性均匀含量降低了95％。在该部分研究中入学的患者也进行了突变分析。 4。该部分的成员被诊断并描述了三名不同的唾液酸代谢疾病的患者，即salla疾病和婴儿游离唾液酸储存疾病。这些疾病是由缺陷的锡林（溶酶体膜转运蛋白）引起的，该蛋白将唾液酸从溶酶体中携带出来。 5。该部分还研究了选定的罕见病患者，包括两名患有灰色血小板综合征的患者，三个患有遗传性纳入身体肌病。在培养的成纤维细胞中测定了后一种疾病中的不足酶UDP-GLCNAC 2- epimerase。对患者也进行了突变分析？脱氧核糖核酸。启动了方案以找到引起灰色血小板综合征的基因，并记录常染色体隐性多囊肾脏疾病和先天性肝纤维化的自然史。