Berry-Kravis E, Huttenlocher P R
Department of Pediatrics, University of Chicago, IL.
Ann Neurol. 1992 Jan;31(1):22-6. doi: 10.1002/ana.410310105.
Cyclic AMP (cAMP) metabolism was studied in platelets from a series of 14 patients with fragile X syndrome (fra X) and 21 control individuals. 1-Isobutyl-3-methylxanthine was used to inhibit phosphodiesterase and thus measure cAMP production, prostaglandin E1 was used to assess receptor-mediated cAMP accumulation, and forskolin was used to directly stimulate the catalytic subunit. In patients with fra X, basal production was 63% of that of control subjects (p = 0.019). Prostaglandin E1- and forskolin-stimulated production were 61% (p = 0.039) and 56% (p = 0.012) of that of control subjects, respectively. cAMP production in 8 patients with fra X overlapped the control range, whereas measures of production in 6 patients formed a cluster with values lower than any of the 21 control subjects assayed, suggesting possible biochemical heterogeneity within patients with fra X. Results obtained from the group of patients with fra X suggest possible abnormal function or regulation of the catalytic subunit of adenylate cyclase in at least a subgroup of patients with fra X. Variability of biochemical findings in patients with fra X may reflect the known high variability of the clinical syndrome.
对14名脆性X综合征（fra X）患者和21名对照个体的血小板中的环磷酸腺苷（cAMP）代谢进行了研究。使用1-异丁基-3-甲基黄嘌呤抑制磷酸二酯酶，从而测量cAMP的产生；使用前列腺素E1评估受体介导的cAMP积累；使用福斯高林直接刺激催化亚基。在fra X患者中，基础产量是对照受试者的63%（p = 0.019）。前列腺素E1和福斯高林刺激的产量分别是对照受试者的61%（p = 0.039）和56%（p = 0.012）。8名fra X患者的cAMP产量落在对照范围内，而6名患者的产量测量值形成一个集群，其值低于所检测的21名对照受试者中的任何一个，这表明fra X患者可能存在生化异质性。从fra X患者组获得的结果表明，至少在一部分fra X患者中，腺苷酸环化酶催化亚基可能存在功能异常或调节异常。fra X患者生化结果的变异性可能反映了已知的临床综合征的高变异性。
