Hommel Angela, Haupt Florian, Delivani Petrina, Winkler Christiane, Stopsack Marina, Wimberger Pauline, Nitzsche Katharina, Heinke Sophie, Naeke Andrea, Ceglarek Uta, Thiery Joachim, Bergert Renate, Stadthaus Daniel, Groeger Katrin, Heubner Georg, Schramm Ursula, Dziambor Ullrich, Zirkel Agnes, Kiess Wieland, Mueller Iris, Lange Karin, Berner Reinhard, Bonifacio Ezio, Ziegler Anette-Gabriele
DFG-Center for Regenerative Therapies Dresden, Faculty of Medicine, TU Dresden - AG Bonifacio, Dresden, Germany.
Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
Horm Metab Res. 2018 Jan;50(1):44-49. doi: 10.1055/s-0043-120921. Epub 2017 Nov 9.
An increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB103 (DR3), HLA DRB104 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.
利用基因和免疫标志物可以识别出1型糖尿病风险增加的情况。弗雷德里克研究在新生儿筛查的背景下引入了1型糖尿病风险的基因检测，以识别有高风险患1型糖尿病的新生儿，以便进行1型糖尿病早期阶段的后续检测和初级预防试验。在新生儿筛查时获得基于研究的1型糖尿病风险基因检测的同意。使用针对HLA DRB103（DR3）、HLA DRB104（DR4）、HLA DQB1*0302（DQ8）等位基因的三个单核苷酸多态性来评估风险增加情况，并定义为：1. HLA DR3/DR4-DQ8或DR4-DQ8/DR4-DQ8基因型；2. HLA DR4-DQ8单倍型以及1型糖尿病的一级家族史。风险增加的婴儿家庭被要求在婴儿6个月、2岁和4岁时参加随访，进行自身抗体检测和1型糖尿病的早期诊断。8个月后，筛查率达到每周181例，弗雷德里克诊所内新生儿覆盖率为63%，萨克森州所有登记出生人口的覆盖率为24%。在4178名接受筛查的婴儿中，2.6%被确定风险增加，约80%符合条件的婴儿被招募进行随访。对符合条件的家庭的心理评估正在进行，31个家庭中没有一个表现出因了解1型糖尿病风险而产生过度负担的迹象。这项试点研究表明，在新生儿筛查项目的背景下对儿童疾病进行基因风险检测是可行的。
