Sagen J V, Baumann M E, Salvesen H B, Molven A, Søvik O, Njølstad P R
Section of Paediatrics, Institute of Clinical Medicine, University of Bergen, Bergen, Norway.
Diabet Med. 2005 Aug;22(8):1012-5. doi: 10.1111/j.1464-5491.2005.01565.x.
Diagnostic screening of NEUROD1 in patients with maturity-onset diabetes of the young (MODY) without mutations in the known MODY-genes (MODYX) and in subjects diagnosed with gestational diabetes mellitus.
Direct sequencing of NEUROD1 was performed in (i) 73 probands with clinical MODY without mutations in hepatocyte nuclear factor (HNF)-4alpha (MODY1), glucokinase (MODY2) and hepatocyte nuclear factor (HNF)-1alpha (MODY3), and (ii) 51 subjects diagnosed with gestational diabetes. Control material consisted of 105 anonymous blood donors.
Mean age at diagnosis of diabetes was 22 and 30 years in the MODYX patients and gestational diabetes mellitus subjects, respectively. Mean fasting blood glucose (9.6 +/- 4.3 vs. 5.7 +/- 1.0 mml/l) as well as glycosylated haemoglobin (8.2 +/- 2.4 vs. 6.0 +/- 0.6%) were higher in the MODYX patients than subjects with gestational diabetes. NEUROD1 mutations were not detected in our two study groups. Three previously reported polymorphisms were found: Ala45Thr, Pro197His and IVS1 -32 nt C>T. The amino acid substitution serine to cysteine in codon 29 (designated Ser29Cys) was detected in one out of 105 control subjects. As the control material consisted of anonymous blood donors, we were prevented from investigation of possible co-segregation between the sequence variant Ser29Cys and diabetes mellitus.
As we found no NEUROD1 mutations, diagnostic screening for this gene is not warranted in Norwegian MODYX patients. Our study also suggests that NEUROD1 is not a candidate gene in gestational diabetes mellitus (GDM). The sequence variant Ser29Cys was identified in one anonymous DNA sample, but we were prevented from studying possible co-segregation with diabetes mellitus.
对已知青年发病型糖尿病（MODY）相关基因（MODYX）无突变的青年发病型糖尿病患者以及被诊断为妊娠期糖尿病的患者进行NEUROD1基因的诊断性筛查。
对以下人群进行NEUROD1基因的直接测序：（i）73例临床诊断为MODY且肝细胞核因子（HNF）-4α（MODY1）、葡萄糖激酶（MODY2）和肝细胞核因子（HNF）-1α（MODY3）无突变的先证者；（ii）51例被诊断为妊娠期糖尿病的患者。对照材料为105名匿名献血者的血液。
MODYX患者和妊娠期糖尿病患者诊断糖尿病时的平均年龄分别为22岁和30岁。MODYX患者的平均空腹血糖（9.6±4.3 vs. 5.7±1.0 mmol/L）以及糖化血红蛋白（8.2±2.4 vs. 6.0±0.6%）均高于妊娠期糖尿病患者。在我们的两个研究组中均未检测到NEUROD1基因突变。发现了三个先前报道的多态性：Ala45Thr、Pro197His和IVS1 -32 nt C>T。在105名对照受试者中的1名中检测到密码子29处丝氨酸到半胱氨酸的氨基酸替换（命名为Ser29Cys）。由于对照材料为匿名献血者的血液，我们无法研究序列变异Ser29Cys与糖尿病之间可能的共分离情况。
由于我们未发现NEUROD1基因突变，因此在挪威MODYX患者中对该基因进行诊断性筛查并无必要。我们的研究还表明，NEUROD1不是妊娠期糖尿病（GDM）的候选基因。在一份匿名DNA样本中鉴定出序列变异Ser29Cys，但我们无法研究其与糖尿病之间可能的共分离情况。
