Transient neonatal diabetes - Widening the understanding of the etiopathogenesis of diabetes
Transient neonatal diabetes - Widening the understanding of the etiopathogenesis of diabetes
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DOI：
10.2337/diabetes.49.8.1359
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发表时间：
2000-08-01
期刊：
影响因子：
7.7
通讯作者：
Shield, JPH
中科院分区：
文献类型：
--
作者：
Temple, IK;Gardner, RJ;Shield, JPH
暂时性新生儿糖尿病 (TND) 是一种罕见的糖尿病，出生后不久就会出现，18 个月后就会消退，并且在以后的生活中容易患上糖尿病。总共对 30 名患者的 6 号染色体畸变进行了确定和调查。还进行了基因型/表型研究。从基因角度来看，这些患者可分为 4 个病因组。第1组为父系单亲6号染色体异二体（11例，其中1对同卵双胞胎）。第 2 组存在涉及染色体带 6q24 的重复，在测试中该重复是父系起源（4 例散发病例和 7 例来自 2 个家庭的家族病例）。第 3 组包括 1 名 TND 关键区域内 CpG 岛甲基化缺失的患者（1 名散发病例）。第 4 组没有可识别的 6 号染色体重排（7 例散发病例）。大多数患者出生时生长迟缓，中位年龄 3 天就诊，中位年龄 12 周康复。在第 2 组中，TND 患者的 2 名亲属患有 2 型糖尿病且没有早期 TND 病史，遗传了相同的重复。大约 70% 的散发性 TND 病例和所有家族病例中都发现了 6 号染色体异常。 4个病因组之间没有发现显着的临床差异。该研究扩大了 TND 的临床范围，将晚年出现的 2 型糖尿病纳入其中，但新生儿没有出现这种情况。这些发现与映射到 6q24 的糖尿病印记基因一致，我们预测该基因将在正常胰腺发育中发挥重要作用。
Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberrations of chromosome 6. A genotype/phenotype study was also performed. Genotypically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome band 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were growth retarded at birth, presented at a median age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented with type 2 diabetes and no early history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in similar to 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal presentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in normal pancreatic development.