Chou Y H, Pollak M R, Brandi M L, Toss G, Arnqvist H, Atkinson A B, Papapoulos S E, Marx S, Brown E M, Seidman J G
Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Am J Hum Genet. 1995 May;56(5):1075-9.
We report five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln, 139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a nonconservative amino acid alteration. These mutations are each predicted to be in the Ca(2+)-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor gene can cause FHH.
我们报告了人类钙离子敏感受体基因中的五个新突变，这些突变导致家族性低钙血症性高钙血症（FHH）或新生儿重症甲状旁腺功能亢进症。每个基因缺陷都是错义突变（228位精氨酸→谷氨酰胺、139位苏氨酸→甲硫氨酸、144位甘氨酸→谷氨酸、63位精氨酸→甲硫氨酸和67位精氨酸→半胱氨酸），编码一种非保守氨基酸改变。这些突变预计均位于钙离子敏感受体的大细胞外结构域。在三个与3号染色体上钙离子敏感受体基因连锁的FHH家族以及FHH的无关先证者个体中，在蛋白质编码序列中未检测到突变。基于这些数据和先前的分析，我们认为存在多种导致FHH的突变。扰乱受体细胞外或跨膜结构域结构和功能的突变以及影响钙离子敏感受体基因非编码序列的突变均可导致FHH。
