Human Biochemical Genetics

人类生物化学遗传学部分研究选择的先天性代谢错误，以提供对细胞机制的洞察和对被遗弃患者群体的护理。1. Hermansky-Pudlak综合征（HPS）是一种罕见的眼部皮肤白化病和出血疾病，由黑素体和血小板致密体的异常形成引起。这种疾病有7种遗传亚型。在过去的一年中，该部门的成员描述了一名患有HPS-4的斯里兰卡患者，HPS-3患者的轻微眼部发现，HPS-5的细胞和临床特征，培养中HPS-3黑色素细胞的细胞内异常运输，以及HPS小鼠模型中称为色素沉着减少的遗传缺陷。他们继续确定HPS亚型临床参与的自然历史，并对这些疾病中细胞内囊泡的运动进行细胞生物学研究。2. 该科的成员在临床中心接收了大约60名胱氨酸病患者，他们接受了半胱胺治疗，并记录了该疾病的非肾脏并发症的存在或不存在。报道了一种基于fish的诊断测试，用于检测胱氨酸病基因CTNS中常见的57-kb缺失。该科成员与国家眼科研究所合作，继续研究治疗角膜胱氨酸晶体的半胱胺滴眼液。3. 该科扩大了其在尿酸症方面的专业知识，尿酸症是由于缺乏均质酸1,2-双加氧酶而导致的均质酸积累紊乱。几个携带假诊断为尿酸尿的病人被该科的成员报告为二甲胺环素引起的色素沉着过度。突变分析也在尿尿患者中进行。S临床研究。4. 该科成员报告了一名患有中度严重游离唾液酸代谢紊乱的患者，类似于Salla病或婴儿游离唾液酸储存病。这些疾病是由唾液素缺陷引起的，唾液素是溶酶体膜运输蛋白，将游离唾液酸从溶酶体中运送出来。5. 该组成员分离并鉴定了哈特纳普病中突变的基因（SLC6A19），哈特纳普病是一种肾小管和肠粘膜上皮质膜转运中性氨基酸的缺陷。6. 本节还报道了遗传性包涵体肌病患者由于GNE基因突变导致的α -三磷酸腺苷异常糖基化，并报道了一例由于SGLT2基因突变导致的肾性血糖升高。7. 该科继续研究灰色血小板综合征（在自然史和基因发现方案中）和常染色体隐性多囊肾病和先天性肝纤维化（定义自然史并确定治疗干预的结果参数）。NHGRI机构审查委员会批准了一项新的临床方案来研究Hutchinson-Gilford早衰综合征的自然史。

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. In the past year, members of the Section described a Sri Lankan patient with HPS-4, mild ocular findings in HPS-3 patients, the cellular and clinical characterization of HPS-5, abnormal intracellular trafficking in HPS-3 melanocytes in culture, and the genetic defect in a mouse model of HPS called reduced pigmentation. They 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. Members of the Section admitted approximately 60 cystinosis patients to the Clinical Center, following their treatment with cysteamine and documenting the presence or absence of nonrenal complications of the disorder. A FISH-based diagnostic test for detection of the common 57-kb deletion in the cystinosis gene, CTNS, was reported. 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. Several patients carrying the false diagnosis of alkaptonuria were reported by members of the Section to have minocycline-induced hyperpigmentation instead. Mutation analysis was also performed in alkaptonuria patients enrolled in the Section?s clinical studies. 4. Members of the Section reported a patient with a moderately severe disorder of free sialic acid metabolism resembling Salla disease or Infantile Free Sialic Acid Storage Disease. These disorders results from defective sialin, the lysosomal membrane transport protein that carries free sialic acid out of lysosomes. 5. Members of the Section isolated and identified the gene (SLC6A19) mutated in Hartnup disorder, a defect of renal tubule and intestinal mucosa epithelial plasma membrane transport of neutral amino acids. 6. The Section also reported hypoglycosylation of alpha-dystroglycan in patients with hereditary inclusion body myopathy due to mutations in the GNE gene, and described a patient with renal glucosuria due to mutations in SGLT2. 7. The Section continues to study Gray Platelet Syndrome (in natural history and gene-finding protocols) and Autosomal Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis (to define the natural history and determine outcome parameters for therapeutic intervention). A new clinical protocol to study the natural history of Hutchinson-Gilford Progeria syndrome has been approved by the NHGRI Institutional Review Board.