A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands

Abstract

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.

Undiagnosed MODY: Time for Action

“…As genetic testing for MODY increased over the span of the study, more cases were discovered and the average age of referral for testing increased in HNF1A -MODY cases (25.7 during 2003–2004 to 29.2 during 2009–2010, p=0.022). (26) These examples of centralized monogenic diabetes testing facilities allow relatively comprehensive population studies regarding the patient characteristics, physician criteria, and testing outcome dynamics of MODY diagnosis.…”

Monogenic diabetes: Implementation of translational genomic research towards precision medicine

“…From a retrospective study in the UK population (between 1996 and 2009), the prevalence of MODY was reported to be approximately 100 cases per 10 6 population, with a large variability among UK provinces . Other estimates from population‐based childhood diabetes registries range between 2.5–5 cases per 100 000 in several European countries and 2.1 cases per 100 000 in American children from the SEARCH for Diabetes in Youth Study . A high frequency (>20 %) of clinically suspected MODY was reported among patients with T2D younger than 25 years of age in south India, but no genetic characterization was performed.…”

Maturity onset diabetes of the young: Diagnosis and treatment options

“…The minimum prevalence of MODY was reported to be 1.1-4.2% of patients with diabetes or 2.4-4.6 cases per 100,000 [9][10][11][12][13][14][15][16]. In Russian population the frequency of MODY 2 and MODY 3 possibly are the same unlike in other countries [17].…”

“…All of the curent data show that MODY is distributed unequally in different countries thus each country should perform its own population studies in order to determine the prevalence of the disease in the population [9][10][11][12].…”