title: 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.
authors.affiliation: Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Weinreich
authors.affiliation: Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bosma
authors.affiliation: Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lidewij
authors.initials: L
authors.lastname: Henneman
authors.affiliation: Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tessel
authors.initials: T
authors.lastname: Rigter
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carla M J
authors.initials: CM
authors.lastname: Spruijt
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anneliese J E M A
authors.initials: AJ
authors.lastname: Grimbergen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.affiliation: Department of Endocrinology and Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.affiliation: Department of Clinical Genetics, Section of Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martina C
authors.initials: MC
authors.lastname: Cornel
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
references.citation: Eur J Hum Genet. 2011 Apr;19 Suppl 1:S6-44
references.pmid: 21412252
references.citation: Lancet. 2003 Oct 18;362(9392):1275-81
references.pmid: 14575972
references.citation: Diabet Med. 2009 Jan;26(1):14-8
references.pmid: 19125755
references.citation: Clin Endocrinol (Oxf). 2011 Oct;75(4):422-6
references.pmid: 21521318
references.citation: Nat Clin Pract Endocrinol Metab. 2008 Apr;4(4):200-13
references.pmid: 18301398
references.citation: Ann Med. 2002;34(3):207-16
references.pmid: 12173691
references.citation: Clin Endocrinol (Oxf). 2007 Oct;67(4):538-46
references.pmid: 17573900
references.citation: Ned Tijdschr Geneeskd. 2005 Jan 15;149(3):139-43
references.pmid: 15693590
references.citation: PLoS One. 2012;7(6):e37423
references.pmid: 22701567
references.citation: Diabetologia. 2010 Dec;53(12):2504-8
references.pmid: 20499044
references.citation: Lancet. 1995 Mar 11;345(8950):648
references.pmid: 7898196
references.citation: Eur J Hum Genet. 2014 Sep;22(9):
references.pmid: 24518839
references.citation: J Clin Endocrinol Metab. 2011 Aug;96(8):E1346-51
references.pmid: 21677039
references.citation: Ned Tijdschr Geneeskd. 2001 Jul 14;145(28):1352-3
references.pmid: 11484433
references.citation: Diabetologia. 2012 Oct;55(10):2631-2635
references.pmid: 22782286
references.citation: Qual Health Res. 2000 Mar;10(2):242-59
references.pmid: 10788286
references.citation: Endocrinol Metab Clin North Am. 2006 Jun;35(2):371-84, x
references.pmid: 16632099
references.citation: PLoS One. 2012;7(4):e34541
references.pmid: 22493702
references.citation: Scand J Public Health. 2011 Aug;39(6):634-9
references.pmid: 21730009