Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur Lille, Univ. Lille, Lille University Hospital, Lille, France.
Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur Lille, Univ. Lille, Lille University Hospital, Lille, France; Department of Metabolism, Section of Genomics of Common Disease, Imperial College London, London, United Kingdom.
Diabetes Res Clin Pract. 2021 Jan;171:108553. doi: 10.1016/j.diabres.2020.108553. Epub 2020 Nov 24.
Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically.
To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries.
We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data.
Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients.
Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.
单基因糖尿病的诊断对治疗和医疗支出具有重要的临床意义。然而，其在许多国家的流行情况仍需进一步明确，尤其是在南欧、北非和中东地区，这些地区年轻人中的非自身免疫性糖尿病发病率正在急剧上升。
鉴定来自地中海国家的年轻单基因糖尿病患者，并评估各国之间的特点。
我们开展了一项跨国多中心研究，对 204 名无关联的糖尿病患者（诊断时年龄：26.1±9.1 岁）进行了外显子组测序。对 35 个靶向基因中的罕见编码变异进行了致病性评估。使用单向方差分析、卡方检验和混合数据因子分析对数据进行分析。
在 36 名患者中发现了 40 个致病性或可能致病性变异，其中 14 个为新变异，遗传诊断率为 17.6%。大多数病例是由于 GCK、HNF1A、ABCC8 和 HNF4A 变异引起的。我们观察到根据国家的不同，诊断率存在很大差异，与遗传背景有关。研究纳入时较低的体重指数和 HbA1c 以及较少使用胰岛素治疗是致病性变异携带者的特征。在几个患者中，根据遗传诊断结果进行了治疗改变。
我们从几个地中海国家的患者数据中突出了糖尿病广泛的临床和遗传谱，表明广泛的基因检测对于早期发病糖尿病的个性化治疗具有重要意义。
