High Prevalence of Albuminuria Among African-Americans With Short Duration of Diabetes
High Prevalence of Albuminuria Among African-Americans With Short Duration of Diabetes
复制标题
糖尿病病程较短的非洲裔美国人中蛋白尿患病率很高
作者：
L. Thaler;I. El;D. Ziemer;D. Gallina;V. Dunbar;L. Phillips
这两种情况被认为是腺苷酸环化酶刺激性鸟嘌呤核苷酸结合 (Gs) 蛋白相同缺陷的变体，腺苷酸环化酶是甲状旁腺激素和其他激素（如促性腺激素、β-肾上腺素激动剂和促甲状腺素）使用 cAMP 作为细胞内第二信使所必需的。我们描述了两名患有明显 AHO 和迟发性糖尿病的相关女性。两名患者的血清钙水平、甲状旁腺激素水平均正常，并且具有身材矮小、圆脸、肥胖以及第四和第五掌骨和跖骨缩短等特征性躯体特征，与假性 PHP 一致。PHP 和假性 PHP 两种疾病可能发生在同一家族内，并且有越来越多的证据表明基因组印记与该疾病有关 (1)。完全表型表达（AHO和甲状旁腺激素抵抗，如PHP la型）发生在母源传播的病例中，而部分表达（AHO没有甲状旁腺激素抵抗，如假PHP）发生在该基因是父源传播的情况下。我们患者的血统显示遗传自他们的父亲。 2型糖尿病患者存在胰岛素作用缺陷、胰岛素分泌异常、肝葡萄糖生成增多等现象。尽管尚未彻底确定导致这些缺陷的精确途径，但它们可能具有遗传异质性，几个不同基因的突变可能导致高血糖。一些报道的 2 型糖尿病遗传位点已定位在 20q 染色体、7p 染色体、12q 染色体、2 号染色体等上 (2,3)。在大多数 AHO 病例中，已发现 Gs 蛋白 a 亚基（Gsa 蛋白）水平降低。位于染色体 20ql3 上的 Gsa 蛋白基因中的许多失活突变已被描述为这种疾病 (1)，但 del(2)(q37) 也在一些 AHO 患者中被描述 (4)，从而解释了在这种 AHO 疾病中观察到的异质性。 PHP 类型1a 或伪PHP 被假定为Gsa 蛋白问题并且该蛋白由染色体20q13 编码。 2-3.有时，这些疾病可能与不同靶组织对激素和神经递质的抵抗有关，这些激素和神经递质的作用需要刺激腺苷酸环化酶，从而打开钙通道。应该考虑这个Gsa蛋白问题是否会导致糖尿病伴有胰岛素抵抗。当然，这些患有 2 型糖尿病的假 PHP 女性要么在 Gsa 蛋白或附近的基因组中发生突变，导致其易患 2 型糖尿病，要么只是一种巧合现象。需要进一步评估和收集病例来明确假性 PHP 和 2 型糖尿病的可能作用和相互关系。
These two conditions are considered variants of the same defect of the stimulatory guanine nucleotide-binding (Gs) protein of adenylate cyclase, which is necessary for parathyroid hormone and other hormones such as gonadotropin, beta-adrenergic agonist, and thyrotropin to use cAMP as an intracellular second messenger. We described two related women with apparent AHO and late-onset diabetes. Both patients had normal serum calcium levels, normal parathyroid hormone levels, and the characteristic somatic features of short stature, round face, obesity, and shortened fourth and fifth metacarpals and metatarsals, consistent with pseudo-PHP Both disorders, PHP and pseudo-PHP, can occur within the same family, and there is accumulating evidence that genomic imprinting is involved in the disease (1). Full phenotypic expression (AHO and parathyroid hormone resistance, as in PHP type la) occurs in maternally transmitted cases, whereas partial expression (AHO without parathyroid hormone resistance, as in pseudo-PHP) occurs when the gene is paternally transmitted. The pedigree of our patients showed genetic transmission from their father. Patients with type 2 diabetes have defects in insulin action, abnormal insulin secretion, and increased hepatic glucose production. Although precise pathways responsible for these defects have not been thoroughly identified, they are likely to be genetically heterogenous with mutations in several different genes that are able to cause hyperglycemia. Some reported genetic loci for type 2 diabetes have been mapped on chromosome 20q, chromosome 7p, chromosome 12q, chromosome 2, and so forth (2,3). In most cases of AHO, reduced levels of Gs protein a subunit (Gsa protein) have been found. A number of deactivating mutations in the gene for Gsa protein located on chromosome 20ql3 have been described for this disorder (1), but del(2)(q37) has also been described in some AHO patients (4) and thus explains the heterogeneity observed in this AHO disorder. PHP type la or pseudo-PHP is assumed to be a Gsa protein problem and this protein is encoded by chromosome 20ql3. 2-3. Occasionally, these disorders may be associated with resistance of diverse target tissues to hormones and neurotransmitters whose actions require stimulation of adenylate cyclase and thus open calcium channels. It should be considered whether this Gsa protein problem will lead to diabetes with insulin resistance. Certainly, either these pseudo-PHP women with type 2 diabetes have a mutation in the Gsa protein or nearby genome for its susceptibility to type 2 diabetes, or they represent just a phenomenon of coincidence. Further evaluation and collection of cases are necessary to define the possible role and interrelationship of pseudo-PHP and type 2 diabetes.
奥尔布赖特遗传性骨营养不良和 del(2) (q37.3) 发生在四个不相关的个体中。
DOI：
10.1002/ajmg.1320580102
发表时间：
1995
期刊：
American journal of medical genetics
影响因子：
--
作者：
Phelan,MC;Rogers,RC;Clarkson,KB;Bowyer,FP;Levine,MA;Estabrooks,LL;Severson,MC;Dobyns,WB
通讯作者：
Dobyns,WB