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.

Figure 1

Molecular genetic testing for HNF4A, GCK and HNF1A MODY over the years 2001–2010. Solid line: mutations scans (nearly always multiplex testing for HNF4A, GCK and HNF1A). Dashed line: positive mutation scans. Dotted line: tests for known mutations (cascade testing) in HNF4A, GCK and HNF1A.

Figure 2

Characteristics of requesters of genetic testing for HNF1A in early (2003–2004) and later (2009–2010) years of test availability. Light bars show averages for 2003–2004; dark bars show averages for 2009–2010. (a) Specialty of requesting physicians. Paediatricians include paediatric endocrinologists. Category ‘other' includes trainee, other or unknown physicians. Each physician was counted once in the year that he/she requested a test for any patient(s). (b) Type of medical institution requesting testing. Multiple referring physicians from the same institution are counted separately.