GENETICS OF FAMILIAL HYPOCALCIURIC HYPERCALCEMIA

家族性低钙尿性高钙血症是一种 以常染色体显性方式遗传，影响个体 有异常的血钙浓度和排泄物 尿钙含量过低。我们假设 患有这种疾病的患者在一种异常的情况下调节钙 时尚和对钙的这种扰动机制的理解 监管将提供有关这种混乱的重要信息 以及钙稳态的正常机制。的模式。 这种疾病的遗传表明单个基因(S)的突变 是FHH的致病基因，我们建议从分子水平上鉴定该基因 基因技术被用来识别其他基因，当 突变导致疾病。尽管这些技术需要大量的 努力，识别精确基因和突变的好处(S) 对一种特定的疾病负有责任，这一努力是值得的。这个 拟议研究的长期目标是确定(S) 在FHH患者中发生突变，以确定FHH患者的遗传关系 FHH导致另一种钙调节障碍，新生儿严重 甲状旁腺机能亢进(NSHPT) 我们将采取以下方法来鉴定突变(S) 对FHH负责。1)确定FHH是否具有遗传异质性 或同质性疾病，并完善FHH区域的遗传图谱(S)； 2)细化FHH-1区域的物理地图；3)搜索FHH区域 3号染色体的基因片段；4)确定候选基因并 确定它们在FHH受试者中是否发生突变；以及5)确定NSHPT是否 由FHH-1基因座纯合子缺陷所致。

Familial hypocalciuric hypercalcaemia (FHH) is a disorder that is inherited in an autosomal dominant fashion in which affected individuals have abnormally high concentrations of serum calcium and excrete inappropriately low amounts of urinary calcium. We hypothesize that affected individuals with this disorder regulate calcium in an abnormal fashion and that understanding this perturbed mechanism of calcium regulation will provide important information both about this disorder and the normal mechanism of calcium homeostasis. The patterns of inheritance of this disorder suggest that a mutation(s) in a single gene is responsible for FHH, and we propose to identify this gene by molecular genetic techniques that have been used to identify other genes that when mutated cause disease. Although these techniques require significant effort, the benefits of identifying the precise gene and the mutation(s) responsible for a particular disorder make this effort worthwhile. The long term goals of the proposed studies are to identify the gene(s) that is mutated in FHH patients and to determine the genetic relationship of FHH to another disorder of calcium regulation, neonatal severe hyperparathyroidism (NSHPT). We will take the following approaches to identify the mutation(s) responsible for FHH. 1) Determine if FHH is a genetically heterogeneous or homogeneous disorder and refine the genetic map in the FHH region(s); 2) Refine the physical map in the FHH-1 region; 3) Search the FHH region of chromosome 3 for gene segments; 4) Identify candidate genes and determine if they are mutated in FHH subjects; and 5) Determine if NSHPT results from homozygous deficiencies at the FHH-1 locus.