Paediatric Endocrinology, St George's University Hospital NHS Foundation Trust, London, UK.
Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
Pediatr Diabetes. 2019 Jun;20(4):482-485. doi: 10.1111/pedi.12826. Epub 2019 Apr 2.
ABCC8 gene mutations with different inheritance patterns have been well described to cause transient and permanent forms of neonatal diabetes with onset of hyperglycemia commonly before the age of 6 months, and rare cases between 6 and 12 months. However, recent analyses have also demonstrated ABCC8 gene mutations in patients with monogenic diabetes (maturity onset diabetes of the young, MODY), with milder clinical phenotypes and later onset of hyperglycemia. We report two siblings with diabetes mellitus due to a novel homozygous p.(Phe1068Ile) (c.3202T>A) missense mutation of the ABCC8 gene, but significantly different phenotypes. The index case was diagnosed with diabetes due to an incidental finding of hyperglycemia at the age of 3 years, while her younger sibling presented with severe hyperglycemia and hyperosmolar dehydration at the age of 10 weeks. The possibility of a significant discordance in the correlation between genotype and phenotype needs to be taken into account when ABCC8 mutation dependent diabetes occurs within the same family. Genetic screening in children with diabetes from consanguineous family needs consideration, especially in case of negative autoantibodies and early onset of hyperglycemia.
ABCC8 基因突变具有不同的遗传模式，这些突变可导致新生儿糖尿病的短暂和永久性形式，发病时高血糖通常发生在 6 个月之前，极少数病例发生在 6 至 12 个月之间。然而，最近的分析也表明 ABCC8 基因突变也存在于单基因糖尿病（年轻起病的成年型糖尿病，MODY）患者中，这些患者具有更轻微的临床表型和更晚发病的高血糖。我们报告了两例因 ABCC8 基因的新型纯合 p.(Phe1068Ile)（c.3202T>A）错义突变导致的糖尿病同胞患者，但表型显著不同。先证者因 3 岁时偶然发现高血糖而被诊断为糖尿病，而她的弟弟/妹妹在 10 周龄时出现严重高血糖和高渗性脱水。当同一家庭中发生 ABCC8 基因突变依赖性糖尿病时，需要考虑基因型与表型之间的相关性存在显著差异的可能性。对于来自近亲家庭的糖尿病患儿，需要考虑进行基因筛查，尤其是在自身抗体阴性和高血糖早发的情况下。
