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.
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References
Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S : Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010; 53: 2504–2508.
Ledermann HM : Is maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? Lancet 1995; 345: 648.
Vaxillaire M, Froguel P : Genetic basis of maturity-onset diabetes of the young. Endocrinol Metab Clin North Am 2006; 35: 371–384.
Bonnefond A, Philippe J, Durand E et al: Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One 2012; 7: e37423.
Murphy R, Ellard S, Hattersley AT : Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 2008; 4: 200–213.
Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT : Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362: 1275–1281.
Spyer G, Macleod KM, Shepherd M, Ellard S, Hattersley AT : Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation. Diabet Med 2009; 26: 14–18.
Naylor R, Philipson LH : Who should have genetic testing for MODY? Clin Endocrinol (Oxf) 2011; 75: 422–426.
Shepherd M : Genetic testing in maturity onset diabetes of the young (MODY)—practical guidelines for professionals. Pract Diab Int 2003; 20: 108–110.
Baan CA, Schoemaker CG, Jacobs-van der Bruggen MAM et alDiabetes tot 2025. 2009; Available from: http://www.rivm.nl/bibliotheek/rapporten/260322004.html . Accessed on 28 June 2013. p 67..
Hamberg-van Reenen HH (RIVM): Diabetes mellitus: Hoe zijn preventie en zorg georganiseerd? In: Volksgezondheid Toekomst Verkenning, Nationaal Kompas Volksgezondheid. 2011; Available from http://www.nationaalkompas.nl/gezondheid-en-ziekte/ziekten-en-aandoeningen/endocriene-voedings-en-stofwisselingsziekten-en-immuniteitsstoornissen/diabetes-mellitus/diabetes-mellitus-preventie-en-zorg/ Accessed on 28 June 2013..
Dutch National Board for DNA-diagnostics: Overzicht DNA diagnostiek Nederland 2012, Available from: http://www.dnadiagnostiek.nl/zoekenStart_nl.php Accessed on 28 June 2013..
Maassen JA, Lemkes HH, Losekoot M : [From gene to disease; 'maturity-onset diabetes of the young' (MODY), monogenetic inheritable forms of diabetes mellitus]. Ned Tijdschr Geneeskd 2001; 145: 1352–1353.
Losekoot M, Broekman AJ, Breuning MH, de Koning EJP, Romijn JA, Maassen JA : [Molecular diagnosis on indication of maturity onset diabetes of the young; results from 184 patients]. Ned Tijdschr Geneeskd 2005; 149: 139–143.
Estalella I, Rica I, Perez de Nanclares G et al: Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. Clin Endocrinol (Oxf) 2007; 67: 538–546.
Statistics Netherlands. Population; key figures. 2013; Available from http://statline.cbs.nl/StatWeb/publication/?DM=SLEN&PA=37296ENG&D1=0-2,19-21,23-27,52-55,57-68&D2=60&LA=EN&VW=T . Accessed on 28 June 2013..
Fendler W, Borowiec M, Baranowska-Jazwiecka A et al: Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia 2012; 55: 2631–2635.
Statistics Netherlands Bevolking; geslacht, leeftijd en burgerlijke staat, 1 januari. 2013; Available from: http://statline.cbs.nl/StatWeb/publication/?DM=SLNL&PA=7461BEV&D1=a&D2=a&D3=0-100&D4=0,(l-2)-l&VW=T . Accessed on 28 June 2013.
Valentinova L, Beer NL, Stanik J et al: Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia. PLoS One 2012; 7: e34541.
Bellanne-Chantelot C, Levy DJ, Carette C et al: Clinical characteristics and diagnostic criteria of maturity-onset diabetes of the young (MODY) due to molecular anomalies of the HNF1A gene. J Clin Endocrinol Metab 2011; 96: e1346–e1351.
Stride A, Hattersley AT : Different genes, different diabetes: lessons from maturity-onset diabetes of the young. Ann Med 2002; 34: 207–216.
Becker F, van El CG, Ibarreta D et al: Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities. Background Document to the ESHG recommendations on genetic testing and common disorders. Eur J Hum Genet 2011; 19 (Suppl 1): S6–S44.
Aarden E, Van Hoyweghen I, Horstman K : The paradox of public health genomics: definition and diagnosis of familial hypercholesterolaemia in three European countries. Scand J Public Health 2011; 39: 634–639.
Shepherd M, Hattersley AT, Sparkes AC : Predictive genetic testing in diabetes: a case study of Multiple perspectives. Qual Health Res 2000; 10: 242–259.
Colclough K, Saint-Martin C, Timsit J, Ellard S, Bellanné-Chantelot C : Clinical utility gene card for: Maturity-onset diabetes of the young. Eur J Hum Genet 2014, e-pub ahead of print 12 February 2014; doi:10.1038/ejhg.2014.14.
Burton H, Cole T, Farndon P : Genomics in Medicine. Cambridge: PHG Foundation, 2012, ISBN 978-1-907198-10-6.
Acknowledgements
We thank TCTEF van Cronenburg (Leiden University Medical Center) for her help in extracting the data from the Laboratory Information System. The study was funded by The Netherlands Genomics Initiative (Project no. CMSB/CSG I.2h) as part of the programme of the Centre for Society and the Life Sciences and the Centre for Medical Systems Biology in The Netherlands. An abstract of this work was presented at the European Society for Human Genetics 2013, P04.87
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Weinreich, S., Bosma, A., Henneman, L. et al. A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands. Eur J Hum Genet 23, 29–33 (2015). https://doi.org/10.1038/ejhg.2014.59
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DOI: https://doi.org/10.1038/ejhg.2014.59
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