HNF1B deletions in patients with young-onset diabetes but no known renal disease
HNF1B deletions in patients with young-onset diabetes but no known renal disease
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DOI：
10.1111/j.1464-5491.2012.03709.x
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发表时间：
2013-01-01
影响因子：
3.5
通讯作者：
Ellard, S.
中科院分区：
文献类型：
--
作者：
Edghill, E. L.;Stals, K.;Ellard, S.
糖尿病。医学。 30, 114117 (2013) 摘要 目的 肝细胞核因子 1 β (HNF1B) 突变会导致肾囊肿和糖尿病综合征，其中全基因缺失约占病例的 50%。肾脏表型的严重程度各不相同，从与生命不相容的肿大囊性肾到正常的肾脏发育和功能。我们调查了患有糖尿病但无已知肾脏疾病的患者中 HNF1B 缺失的患病率。方法 我们对 461 名 45 岁之前诊断出的家族性糖尿病患者进行了测试，其中包括 258 名符合青少年发病型糖尿病临床标准的先证者（两代人受影响，且至少一名家庭成员在 25 岁以下诊断）。使用荧光聚合酶链反应测定来分析两个基因内多态性 HNF1B 标记，并识别因此没有整个基因缺失的杂合患者。然后使用多重连接依赖性探针扩增测试这些两个标记纯合的患者是否存在 HNF1B 缺失。结果 在 337/461 名受试者中鉴定出杂合 HNF1B 基因内多态性。多重连接依赖性探针扩增分析显示，其余 124 名先证者中的 3 名存在 HNF1B 基因缺失，所有这些先证者均符合青少年发病型糖尿病的标准。对他们亲属的检测发现了另外三名缺失携带者，超声扫描显示这六名患者中的三名出现肾脏发育异常。结论 我们估计，HNF1B 突变在青少年发病的糖尿病病例中所占比例< 1%。尽管在没有已知肾脏疾病的情况下，HNF1B 突变是糖尿病的罕见原因，但肾囊肿和糖尿病综合征的基因诊断很重要，因为它增加了亚临床肾脏疾病的可能性，以及患者后代患肾囊肿和糖尿病综合征的 50% 风险。糖尿病。医学。 30, 114-117 (2013)
Diabet. Med. 30, 114117 (2013) Abstract Aims Hepatocyte nuclear factor 1 beta (HNF1B) mutations cause a syndrome of renal cysts and diabetes, with whole gene deletions accounting for approximately 50% of cases. The severity of the renal phenotype is variable, from enlarged cystic kidneys incompatible with life to normal renal development and function. We investigated the prevalence of HNF1B deletions in patients with diabetes but no known renal disease. Methods We tested 461 patients with familial diabetes diagnosed before 45 years, including 258 probands who met clinical criteria for maturity-onset diabetes of the young (two generations affected and at least one family member diagnosed under 25 years). A fluorescent polymerase chain reaction assay was used to analyse two intragenic polymorphic HNF1B markers and identify heterozygous patients who therefore did not have whole gene deletions. Those patients homozygous for both markers were then tested for an HNF1B deletion using multiplex ligation-dependent probe amplification. Results Heterozygous HNF1B intragenic polymorphisms were identified in 337/461 subjects. Multiplex ligation-dependent probe amplification analysis showed an HNF1B gene deletion in three of the remaining 124 probands, all of whom met the criteria for maturity-onset diabetes of the young. Testing of their relatives identified three additional deletion carriers and ultrasound scanning showed renal developmental abnormalities in three of these six patients. Conclusions We estimate that HNF1B mutations account for < 1% of cases of maturity-onset diabetes of the young. Although HNF1B mutations are a rare cause of diabetes in the absence of known renal disease, a genetic diagnosis of renal cysts and diabetes syndrome is important as it raises the possibility of subclinical renal disease and the 50% risk of renal cysts and diabetes syndrome in the patients offspring. Diabet. Med. 30, 114-117 (2013)