Institute of Child Health, University College London, Great Ormond Street Hospital for Children NHS Trust, London, UK.
Pediatr Diabetes. 2011 May;12(3 Pt 1):192-6. doi: 10.1111/j.1399-5448.2010.00683.x. Epub 2010 Sep 6.
Permanent neonatal diabetes mellitus (PNDM) caused by homozygous mutations in the glucokinase gene (GCK) is rare and only eight homozygous GCK mutations have been reported so far. Heterozygous GCK mutations cause maturity-onset diabetes of the young (MODY). We report four patients with growth retardation from two separate families (with three siblings in one family and one patient in another family) presenting with persistent hyperglycaemia within the first two days of life. We found one homozygous non-sense mutation (Q98X) in GCK in three siblings from one family and a homozygous missense GCK mutation (G261R) in one patient from another family. Both mutations have been identified previously in GCK-MODY in the heterozygous state. However, this is the first study to report the homozygous forms of these mutations in PNDM. We report four novel cases of PNDM caused by homozygous GCK mutations, including a non-sense mutation in exon 3 (Q98X) and a missense mutation in exon 7 (G261R).
由葡萄糖激酶基因（GCK）纯合突变引起的永久性新生儿糖尿病（PNDM）较为罕见，迄今为止仅报道了 8 种纯合 GCK 突变。杂合 GCK 突变导致青年发病的成年型糖尿病（MODY）。我们报告了两例来自两个不同家庭的生长迟缓患者（一个家庭中有三个兄弟姐妹，另一个家庭中有一个患者），他们在出生后前两天内出现持续性高血糖。我们在一个家庭的三个兄弟姐妹中发现了 GCK 的一个纯合无义突变（Q98X），在另一个家庭的一个患者中发现了一个 GCK 的纯合错义突变（G261R）。这两种突变以前在 GCK-MODY 的杂合状态下已经被识别出来。然而，这是首次在 PNDM 中报告这些突变的纯合形式的研究。我们报告了由 GCK 基因突变引起的 4 例新的 PNDM，包括外显子 3 的无义突变（Q98X）和外显子 7 的错义突变（G261R）。
