Schipani E, Kruse K, Jüppner H
Department of Medicine, Massachusetts General Hospital 02114, USA.
Science. 1995 Apr 7;268(5207):98-100. doi: 10.1126/science.7701349.
A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3',5'-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism.
在一名患有詹森型干骺端软骨发育不良的患者中，发现甲状旁腺激素 - 甲状旁腺激素相关肽（PTH - PTHrP）受体编码基因的外显子M2中存在单个杂合核苷酸交换，该交换将受体第一个细胞内环中第223位严格保守的组氨酸残基变为精氨酸。在表达突变型PTH - PTHrP受体的COS - 7细胞中观察到组成性的、不依赖配体的3',5'-环磷酸腺苷积累，而在表达野生型受体的细胞中未观察到。这一发现解释了这种罕见的短肢侏儒症中严重的不依赖配体的高钙血症和低磷血症，以及很可能的软骨内骨异常形成。
