Weinreich Stephanie S, Bosma Astrid, Henneman Lidewij, Rigter Tessel, Spruijt Carla M J, Grimbergen Anneliese J E M A, Breuning Martijn H, de Koning Eelco J P, Losekoot Monique, Cornel Martina C
Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Hum Genet. 2015 Jan;23(1):29-33. doi: 10.1038/ejhg.2014.59. Epub 2014 Apr 16.
Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant for treatment and prognosis in patients with usually early-onset, non-ketotic, insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation carriers. This study describes the first 10 years of genetic testing for MODY in The Netherlands in terms of volume and test positive rate, medical setting, purpose of the test and age of patients tested. Some analyses focus on the most prevalent subtype, HNF1A MODY. Data were retrospectively extracted from a laboratory database. In total, 502 individuals were identified with a pathogenic mutation in HNF4A, GCK or HNF1A between 2001 and 2010. Although mutation scanning for MODY was used at an increasing rate, cascade testing was only used for one relative, on average, per positive index patient. Testing for HNF1A MODY was mostly requested by internists and paediatricians, often from regional hospitals. Primary care physicians and clinical geneticists rarely requested genetic testing for HNF1A MODY. Clinical geneticists requested cascade testing relatively more often than other health professionals. A substantial proportion (currently 29%) of HNF1A MODY probands was at least 40 years old at the time of testing. In conclusion, the number of individuals genetically tested for MODY so far in The Netherlands is low compared with previously predicted numbers of patients. Doctors' valuation of the test and patients' and family members' response to (an offer of) genetic testing on the other hand need to be investigated. Efforts may be needed to develop and implement translational guidelines.
对青年发病的成年型糖尿病（MODY）进行基因检测，可能与通常起病较早、非酮症、胰岛素敏感型糖尿病患者的治疗及预后相关，也与非糖尿病突变携带者的监测策略有关。本研究从检测量和检测阳性率、医疗环境、检测目的及受检患者年龄等方面，描述了荷兰开展MODY基因检测的首个十年情况。部分分析聚焦于最常见的亚型，即肝细胞核因子1α（HNF1A）-MODY。数据从实验室数据库中进行回顾性提取。2001年至2010年间，共识别出502例在肝细胞核因子4α（HNF4A）、葡萄糖激酶（GCK）或HNF1A基因存在致病突变的个体。尽管MODY突变扫描的使用频率不断增加，但级联检测平均每位阳性索引患者仅用于一名亲属。HNF1A-MODY检测大多由内科医生和儿科医生提出，他们常来自地区医院。基层医疗医生和临床遗传学家很少要求对HNF1A-MODY进行基因检测。临床遗传学家要求进行级联检测的频率相对高于其他医疗专业人员。相当一部分（目前为29%）HNF1A-MODY先证者在检测时年龄至少为40岁。总之，与先前预测的患者数量相比，荷兰目前接受MODY基因检测的个体数量较少。另一方面，医生对检测的评估以及患者和家庭成员对基因检测（提议）的反应有待研究。可能需要努力制定和实施转化指南。
